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<ANTIMG class="nc" id="coverpage" src="images/cover.jpg" alt="Radioisotopes in Medicine" width-obs="500" height-obs="782" /></div>
<h1><span class="center">Radioisotopes in Medicine</span></h1>
<p class="tb"><b>The Understanding the Atom Series</b></p>
<p>Nuclear energy is playing a vital role in the life of every
man, woman, and child in the United States today. In the
years ahead it will affect increasingly all the peoples of the
earth. It is essential that all Americans gain an understanding
of this vital force if they are to discharge thoughtfully their
responsibilities as citizens and if they are to realize fully the
myriad benefits that nuclear energy offers them.</p>
<p>The United States Atomic Energy Commission provides
this booklet to help you achieve such understanding.</p>
<div class="fig"> id="pic_1"> <ANTIMG src="images/pmg001.jpg" alt="Edward J. Brunenkant" width-obs="300" height-obs="98" /></div>
<p><span class="lr">Edward J. Brunenkant, Director</span>
<span class="lr">Division of Technical Information</span></p>
<p class="tb">UNITED STATES ATOMIC ENERGY COMMISSION</p>
<dl class="undent"><br/>Dr. Glenn T. Seaborg, Chairman
<br/>James T. Ramey
<br/>Wilfrid E. Johnson
<br/>Dr. Theos J. Thompson
<br/>Dr. Clarence E. Larson
<h1 title="">Radioisotopes in Medicine</h1>
<p class="b ss">by Earl W. Phelan</p>
<h2 title="" class="center">CONTENTS</h2>
<br/><SPAN href="#c1">INTRODUCTION</SPAN> 1
<br/><SPAN href="#c2">History</SPAN> 1
<br/><SPAN href="#c3">What Is Radiation?</SPAN> 5
<br/><SPAN href="#c4">What Is Radioactivity?</SPAN> 5
<br/><SPAN href="#c5">What Are Radioisotopes?</SPAN> 6
<br/><SPAN href="#c6">How Are Radioisotopes Used?</SPAN> 7
<br/><SPAN href="#c7">What Do We Mean by Tracer Atoms?</SPAN> 9
<br/><SPAN href="#c8">DIAGNOSIS</SPAN> 11
<br/><SPAN href="#c9">Pinpointing Disease</SPAN> 11
<br/><SPAN href="#c10">Arsenic-74</SPAN> 14
<br/><SPAN href="#c11">Chromium-51</SPAN> 15
<br/><SPAN href="#c12">Cobalt-60</SPAN> 16
<br/><SPAN href="#c13">Iodine-131</SPAN> 18
<br/><SPAN href="#c14">Iron-59</SPAN> 23
<br/><SPAN href="#c15">Phosphorus-32</SPAN> 24
<br/><SPAN href="#c16">Sodium-24</SPAN> 25
<br/><SPAN href="#c17">Technetium-99<sup><i>m</i></sup></SPAN> 26
<br/><SPAN href="#c18">Thulium-170 and Gamma Radiography</SPAN> 27
<br/><SPAN href="#c19">Tritium</SPAN> 28
<br/><SPAN href="#c20">Activation Analysis</SPAN> 30
<br/><SPAN href="#c21">Summary</SPAN> 30
<br/><SPAN href="#c22">THERAPY</SPAN> 31
<br/><SPAN href="#c23">A Successful Case</SPAN> 31
<br/><SPAN href="#c24">General Principles</SPAN> 32
<br/><SPAN href="#c25">Iodine-131 and Iodine-132</SPAN> 32
<br/><SPAN href="#c26">Boron-10</SPAN> 33
<br/><SPAN href="#c27">Phosphorus-32</SPAN> 35
<br/><SPAN href="#c28">Gold-198</SPAN> 37
<br/><SPAN href="#c29">Beads, Needles, and Applicators</SPAN> 38
<br/><SPAN href="#c30">Teletherapy</SPAN> 41
<br/><SPAN href="#c31">CONCLUSIONS</SPAN> 43
<br/><SPAN href="#c32">APPENDIX</SPAN> 44
<br/><SPAN href="#c33">SUGGESTED REFERENCES</SPAN> 47
<p class="center">United States Atomic Energy Commission
<br/>Division of Technical Information
<br/><span class="smaller">Library of Congress Catalog Card Number: 66-62749
<br/>1966</span></p>
<div class="fig"> id="pic_2"> <ANTIMG src="images/pmg002.jpg" alt="" width-obs="300" height-obs="453" /> <p class="caption small"><b>THE COVER</b></p> <p class="caption small">This multi-detector positron scanner is used to locate tumors. A radioisotope-labeled
substance is injected into the
body and subsequently concentrates in
the tumor tissue. The radioisotope emits
positrons that immediately decay and
produce two gamma rays that travel in
opposite directions. These rays are detected
simultaneously on a pair of opposing
detection crystals and a line is
established along which the tumor is
located. This method is one of many
ways doctors use radioisotopes to combat
disease. In this, as in many other
procedures described in this booklet,
the patient remains comfortable at all
times.</p>
</div>
<div class="fig"> id="pic_3"> <ANTIMG src="images/pmg002a.jpg" alt="" width-obs="500" height-obs="686" /> <p class="caption small"><b>THE AUTHOR</b></p> <p class="caption small"><b>Earl W. Phelan</b> is Professor of Chemistry at Tusculum College,
Greeneville, Tennessee. From 1952
to 1965, he served as Staff Assistant
in the Laboratory Director’s
Office at Argonne National Laboratory,
where his duties included
editing the Argonne Reviews and
supplying information to students.
For 22 years prior to moving to
Argonne he served as Head of the
Chemistry Department of the Valdosta
State College In Georgia. He
received his B.S. and Ph.D. degrees
from Cornell University.</p>
</div>
<div class="pb" id="Page_1">1</div>
<h1 title=""><span class="jr">Radioisotopes in Medicine</span></h1>
<p><span class="lr">By EARL W. PHELAN</span></p>
<h2 id="c1">INTRODUCTION</h2>
<h3 id="c2">History</h3>
<p>The history of the use of radioisotopes for medical
purposes is filled with names of Nobel Prize winners. It
is inspiring to read how great minds attacked puzzling
phenomena, worked out the theoretical and practical implications
of what they observed, and were rewarded by
the highest honor in science.</p>
<p>For example, in 1895 a German
physicist, Wilhelm Konrad
Roentgen, noticed that certain
crystals became luminescent
when they were in the vicinity of
a highly evacuated electric-discharge
tube. Objects placed between
the tube and the crystals
screened out some of the invisible
radiation that caused this effect,
and he observed that the greater
the density of the object so
placed, the greater the screening
effect. He called this new
radiation X rays, because <i>x</i> was the standard algebraic
symbol for an unknown quantity. His discovery won him the
first Nobel Prize in physics in 1901.</p>
<div class="fig"> id="pic_4"> <ANTIMG src="images/pmg002c.jpg" alt="" width-obs="459" height-obs="595" /> <p class="caption small"><i>Wilhelm Roentgen</i></p> </div>
<div class="pb" id="Page_2">2</div>
<p>A French physicist, Antoine Henri
Becquerel, newly appointed to the
chair of physics at the Ecole Polytechnique
in Paris, saw that this discovery
opened up a new field for
research and set to work on some of
its ramifications. One of the evident
features of the production of X rays
was the fact that while they were
being created, the glass of the vacuum
tube gave off a greenish phosphorescent
glow. This suggested to
several physicists that substances which become phosphorescent
upon exposure to visible light might give off
X rays along with the phosphorescence.</p>
<p>Becquerel experimented with this by exposing various
crystals to sunlight and then placing each of them on a
black paper envelope enclosing an unexposed photographic
plate. If any X rays were thus produced, he reasoned, they
would penetrate the wrapping and create a developable spot
of exposure on the plate. To his delight, he indeed observed
just this effect when he used a phosphorescent material,
uranium potassium sulfate. Then he made a confusing discovery.
For several days there was no sunshine, so he
could not expose the phosphorescent material. For no
particular reason (other than that there was nothing else
to do) Becquerel developed a plate that had been in contact
with uranium material in a dark drawer, even though there
had been no phosphorescence. The telltale black spot marking
the position of the mineral nevertheless appeared on the
developed plate! His conclusion was that uranium in its
normal state gave off X rays or something similar.</p>
<div class="fig"> id="pic_5"> <ANTIMG src="images/pmg003.jpg" alt="" width-obs="300" height-obs="386" /> <p class="caption small"><i>Henri Becquerel</i></p> </div>
<p>At this point, Pierre Curie, a friend of Becquerel and
also a professor of physics in Paris, suggested to one of
his graduate students, his young bride, Marie, that she
study this new phenomenon. She found that both uranium
and thorium possessed this property of radioactivity, but
also, surprisingly, that some uranium minerals were more
radioactive than uranium itself. Through a tedious series
of chemical separations, she obtained from pitchblende (a
uranium ore) small amounts of two new elements, polonium
<span class="pb" id="Page_3">3</span>
and radium, and showed that they possessed far greater
radioactivity than uranium itself. For this work Becquerel
and the two Curies were jointly awarded the Nobel Prize
in physics in 1903.</p>
<div class="fig"> id="pic_6"> <ANTIMG src="images/pmg003a.jpg" alt="" width-obs="600" height-obs="339" /> <p class="caption small"><i>Pierre and Marie Curie</i></p> </div>
<p>At the outset, Roentgen had noticed that although X rays
passed through human tissue without causing any immediate
sensation, they definitely affected the skin and underlying
cells. Soon after exposure, it was evident that X rays
could cause redness of the skin, blistering, and even ulceration,
either in single doses or in repeated smaller
doses. In spite of the hazards<SPAN class="fn" id="fr_1" href="#fn_1">[1]</SPAN> involved, early experimenters
determined that X rays could destroy cancer
tissues more rapidly than they affected healthy organs, so
a basis was established quite soon for one of Medicine’s
few methods of curing or at least restraining cancer.</p>
<p>The work of the Curies in turn stimulated many studies
of the effect of radioactivity. It was not long before experimenters
learned that naturally radioactive elements—like
radium—were also useful in cancer therapy. These
elements emitted gamma rays,<SPAN class="fn" id="fr_2" href="#fn_2">[2]</SPAN> which are like X rays but
usually are even more penetrating, and their application
often could be controlled better than X rays. Slowly, over
the years, reliable methods were developed for treatment
with these radioactive sources, and instruments were designed
for measuring the quantity of radiation received by
the patient.</p>
<div class="pb" id="Page_4">4</div>
<div class="fig"> id="pic_7"> <ANTIMG src="images/pmg004.jpg" alt="" width-obs="500" height-obs="333" /> <p class="caption small"><i>Frederic and Irene Joliot-Curie</i></p> </div>
<p>The next momentous advance was made by Frederic
Joliot, a French chemist who married Irene Curie, daughter
of Pierre and Marie Curie. He discovered in 1934 that when
aluminum was bombarded with alpha particles<SPAN class="fn" id="fr_3" href="#fn_3">[3]</SPAN> from a
radioactive source, emission of positrons (positive electrons)
was induced. Moreover, the emission continued long
after the alpha source was removed. This was the first
example of artificially induced radioactivity, and it stimulated
a new flood of discoveries. Frederic and Irene Joliot-Curie
won the Nobel Prize in chemistry in 1935 for this
work.</p>
<p>Others who followed this discovery with the development
of additional ways to create artificial radioactivity were
two Americans, H. Richard Crane and C. C. Lauritsen, the
British scientists, John Cockcroft and E. T. S. Walton, and
an American, Robert J. Van de Graaff. Ernest O. Lawrence,
an American physicist, invented the cyclotron (or “atom
smasher”), a powerful source of high-energy particles that
induced radioactivity in whatever target materials they impinged
upon. Enrico Fermi, an Italian physicist, seized
upon the idea of using the newly discovered neutron (an
electrically neutral particle) and showed that bombardment
with neutrons also could induce radioactivity in a target
substance. Cockcroft and Walton, Lawrence, and Fermi all
won Nobel Prizes for their work.</p>
<div class="pb" id="Page_5">5</div>
<p>Patient application of these new sources of bombarding
particles resulted in the creation of small quantities of
hundreds of radioactive isotopic species, each with distinctive
characteristics. In turn, as we shall see, many
ways to use radioisotopes have been developed in medical
therapy, diagnosis, and research. By now, more than 3000
hospitals hold licenses from the Atomic Energy Commission
to use radioisotopes. In addition, many thousands of
doctors, dentists, and hospitals have X-ray machines that
they use for some of the same broad purposes. One of the
results of all this is that every month new uses of radioisotopes
are developed.</p>
<p>More persons are trained every year in methods of
radioisotope use and more manufacturers are producing
and packaging radioactive materials. This booklet tells
some of the successes achieved with these materials for
medical purposes.</p>
<h3 id="c3">What Is Radiation?</h3>
<p>Radiation is the propagation of radiant energy in the
form of waves or particles. It includes electromagnetic
radiation ranging from radio waves, infrared heat waves,
visible light, ultraviolet light, and X rays to gamma rays.
It may also include beams of particles of which electrons,
positrons, neutrons, protons, deuterons, and alpha particles
are the best known.<SPAN class="fn" id="fr_4" href="#fn_4">[4]</SPAN></p>
<h3 id="c4">What Is Radioactivity?</h3>
<p>It took several years following the basic discovery by
Becquerel, and the work of many investigators, to systematize
the information about this phenomenon. Radioactivity
is defined as the property, possessed by some materials,
of spontaneously emitting alpha or beta particles or gamma
rays as the unstable (or radioactive) nuclei of their atoms
disintegrate.</p>
<div class="pb" id="Page_6">6</div>
<h3 id="c5">What Are Radioisotopes?</h3>
<div class="fig"> id="pic_8"> <ANTIMG src="images/pmg005.jpg" alt="" width-obs="500" height-obs="620" /> <p class="caption small"><i>Frederick Soddy</i></p> </div>
<p>In the 19th Century an Englishman,
John Dalton, put forth his
atomic theory, which stated that
all atoms of the same element
were exactly alike. This remained
unchallenged for 100 years, until
experiments by the British chemist,
Frederick Soddy, proved conclusively
that the element neon
consisted of two different kinds of
atoms. All were alike in chemical
behavior but some had an atomic weight (their mass
relative to other atoms) of 20 and some a weight of 22.
He coined the word <i>isotope</i> to describe one of two or more
atoms having the same atomic number but different atomic
weights.<SPAN class="fn" id="fr_5" href="#fn_5">[5]</SPAN></p>
<p>Radioisotopes are isotopes that are unstable, or radioactive,
and give off radiation spontaneously. Many radioisotopes
are produced by bombarding suitable targets with
neutrons now readily available inside atomic reactors.
Some of them, however, are more satisfactorily created by
the action of protons, deuterons, or other subatomic particles
that have been given high velocities in a cyclotron
or similar accelerator.</p>
<p>Radioactivity is a process that is practically uninfluenced
by any of the factors, such as temperature and pressure,
that are used to control the rate of chemical reactions. The
rate of radioactive decay appears to be affected only by
the structure of the unstable (decaying) nucleus. Each
radioisotope has its own half-life, which is the time it
takes for one half the number of atoms present to decay.
These half-lives vary from fractions of a second to millions
of years, depending only upon the atom. We shall see that
the half-life is one factor considered in choosing a particular
isotope for certain uses.</p>
<div class="pb" id="Page_7">7</div>
<div class="fig"> id="pic_9"> <ANTIMG src="images/pmg005a.jpg" alt="" width-obs="500" height-obs="259" /> <p class="caption small"><b>HALF-LIFE PATTERN OF STRONTIUM-90</b></p> </div>
<p>Most artificially made radioisotopes have relatively
short half-lives. This makes them useful in two ways.
First, it means that very little material is needed to obtain
a significant number of disintegrations. It should be
evident that, with any given number of radioactive atoms,
the number of disintegrations per second will be inversely
proportional to the half-life. Second, by the time 10 half-lives
have elapsed, the number of disintegrations per second
will have dwindled to ¹/₁₀₂₄ the original number, and the
amount of radioactive material is so small it is usually no
longer significant. (Note the decrease in the figure above.)</p>
<h3 id="c6">How Are Radioisotopes Used?</h3>
<p>A radioisotope may be used either as a source of radiation
energy (energy is <i>always</i> released during decay), or
as a tracer: an identifying and readily detectable marker
material. The location of this material during a given
treatment can be determined with a suitable instrument
even though an unweighably small amount of it is present
in a mixture with other materials. On the following pages
we will discuss medical uses of individual radioisotopes—first
those used as tracers and then those used for their
energy. In general, tracers are used for analysis and
<span class="pb" id="Page_8">8</span>
diagnosis, and radiant-energy emitters are used for treatment
(therapy).</p>
<p>Radioisotopes offer two advantages. First, they can be
used in extremely small amounts. As little as one-billionth
of a gram can be measured with suitable apparatus. Secondly,
they can be directed to various definitely known
parts of the body. For example, radioactive sodium iodide
behaves in the body just the same as normal sodium iodide
found in the iodized salt used in many homes. The iodine
concentrates in the thyroid gland where it is converted to
the hormone thyroxin. Other radioactive, or “tagged”,
atoms can be routed to bone marrow, red blood cells, the
liver, the kidneys, or made to remain in the blood stream,
where they are measured using suitable instruments.<SPAN class="fn" id="fr_6" href="#fn_6">[6]</SPAN></p>
<p>Of the three types of radiation, alpha particles (helium
nuclei) are of such low penetrating power that they cannot
be used for measurement from outside the body. Beta
particles (electrons) have a moderate penetrating power,
therefore they produce useful therapeutic results in the
vicinity of their release, and they can be detected by
sensitive counting devices. Gamma rays are highly energetic,
and they can be readily detected by counters—radiation
measurement devices—used outside the body.</p>
<div class="fig"> id="pic_10"> <ANTIMG src="images/pmg006.jpg" alt="" width-obs="500" height-obs="194" /> <p class="caption small"><i>Relative penetration of alpha, beta, and gamma radiation.</i></p> </div>
<p>For comparison, a sheet of paper stops alpha particles, a
block of wood stops beta particles, and a thick concrete
wall stops gamma rays.</p>
<div class="pb" id="Page_9">9</div>
<p>In one way or another, the key to the usefulness of radioisotopes
lies in the energy of the radiation. When radiation
is used for treatment, the energy absorbed by the body is
used either to destroy tissue, particularly cancer, or to
suppress some function of the body. Properly calculated
and applied doses of radiation can be used to produce the
desired effect with minimum side reactions. Expressed in
terms of the usual work or heat units, ergs or calories,
the amount of energy associated with a radiation dose is
small. The significance lies in the fact that this energy is
released in such a way as to produce important changes
in the molecular composition of individual cells within
the body.</p>
<h3 id="c7">What Do We Mean by Tracer Atoms?</h3>
<p>When a radioisotope is used as a tracer, the energy of
the radiation triggers the counting device, and the exact
amount of energy from each disintegrating atom is measured.
This differentiates the substance being traced from
other materials naturally present.</p>
<div class="fig"> id="pic_11"> <ANTIMG src="images/pmg006a.jpg" alt="" width-obs="600" height-obs="340" /> <p class="caption small"><i>This is the first photoscanner, which was developed in 1954 at the University of Pennsylvania and was retired from service in 1963. When gamma rays emitted by a tracer isotope in the patient’s body
struck the scanner, a flashing light produced a dot on photographic
film. The intensity of the light varied with the counting rate and
thus diseased tissues that differed little from normal tissue except
in their uptake of an isotope could be discerned.</i></p>
</div>
<div class="pb" id="Page_10">10</div>
<p>With one conspicuous exception, it is impossible for a
chemist to distinguish any one atom of an element from
another. Once ordinary salt gets into the blood stream,
for example, it normally has no characteristic by which
anyone can decide what its source was, or which sodium
atoms were added to the blood and which were already
present. The exception to this is the case in which some
of the atoms are “tagged” by being made radioactive. Then
the radioactive atoms are readily identified and their
quantity can be measured with a counting device.</p>
<p>A radioactive tracer, it is apparent, corresponds in
chemical nature and behavior to the thing it traces. It is
a true part of it, and the body treats the tagged and untagged
material in the same way. A molecule of hemoglobin
carrying a radioactive iron atom is still hemoglobin, and
the body processes affect it just as they do an untagged
hemoglobin molecule. The difference is that a scientist can
use counting devices to follow the tracer molecules wherever
they go.</p>
<div class="fig"> id="pic_12"> <ANTIMG src="images/pmg007.jpg" alt="" width-obs="500" height-obs="329" /> <p class="caption small"><i>One of the first scans made by a photoscanner. The photorecording (dark bands), superimposed on an X-ray picture for orientation, shows radioactivity in a cancer in the patient’s neck.</i></p>
</div>
<p>It should be evident that tracers used in <i>diagnosis</i>—to
identify disease or improper body function—are present in
such small quantities that they are relatively harmless.
<span class="pb" id="Page_11">11</span>
Their effects are analogous to those from the radiation
that every one of us continually receives from natural
sources within and without the body. <i>Therapeutic</i> doses—those
given for medical treatment—by contrast, are
given to patients with a disease that is in need of control,
that is, the physician desires to destroy selectively cells
or tissues that are abnormal. In these cases, therefore,
the skill and experience of the attending physician must be
applied to limit the effects to the desired benefits, without
damage to healthy organs.</p>
<p>This booklet is devoted to these two functions of radioisotopes,
<i>diagnosis</i> and <i>therapy</i>; the field of medical research
using radioactive tools is so large that it requires
separate coverage.<SPAN class="fn" id="fr_7" href="#fn_7">[7]</SPAN></p>
<h2 id="c8">DIAGNOSIS</h2>
<h3 id="c9">Pinpointing Disease</h3>
<p>Mr. Peters, 35-year-old father of four and a resident
of Chicago’s northwest side, went to a Chicago hospital
one winter day after persistent headaches had made his
life miserable. Routine examinations showed nothing amiss
and his doctor ordered a “brain scan” in the hospital’s
department of nuclear medicine.</p>
<p>Thirty minutes before “scan time”, Mr. Peters was
given, by intravenous injection, a minute amount of radioactive
technetium. This radiochemical had been structured
so that, if there were a tumor in his cranium, the
radioisotopes would be attracted to it. Then he was positioned
so an instrument called a scanner could pass
close to his head.</p>
<p>As the motor-driven scanner passed back and forth, it
picked up the gamma rays being emitted by the radioactive
technetium, much as a Geiger counter detects other
radiation. These rays were recorded as black blocks on
sensitized film inside the scanner. The result was a piece
of exposed film that, when developed, bore an architectural
likeness or image of Mr. Peters’ cranium.</p>
<div class="pb" id="Page_12">12</div>
<div class="fig"> id="pic_13"> <ANTIMG src="images/pmg008.jpg" alt="" width-obs="500" height-obs="403" /> <p class="caption small"><i>The inset picture shows a brain scan made with a positron scintillation camera. A tumor is indicated by light area above ear. (Light area in facial region is caused by uptake in bone and extracellular
space.) The photograph shows a patient, completely comfortable,
receiving a brain scan on one of the three rectilinear scanning devices
in the nuclear medicine laboratory of a hospital.</i></p>
</div>
<p>Mr. Peters, who admitted to no pain or other adverse
reaction from the scanning, was photographed by the
scanner from the front and both sides. The procedure took
less than an hour. The developed film showed that the
technetium had concentrated in one spot, indicating definitely
that a tumor was present. Comparison of front and
side views made it possible to pinpoint the location exactly.</p>
<p>Surgery followed to remove the tumor. Today, thanks
to sound and early diagnosis, Mr. Peters is well and back
on the job. His case is an example of how radioisotopes
are used in hospitals and medical centers for diagnosis.</p>
<div class="pb" id="Page_13">13</div>
<div class="fig"> id="pic_14"> <ANTIMG src="images/pmg008a.jpg" alt="" width-obs="500" height-obs="396" /> <p class="caption small"><i>The first whole body scanner, which was developed at the Donner Laboratory in 1952 and is still being used. The lead collimator contains 10 scintillation counters and moves across the subject.
The bed is moved and serial scans are made and then joined together
to form a head-to-toe picture of the subject.</i></p>
</div>
<div class="fig"> id="pic_15"> <ANTIMG src="images/pmg008b.jpg" alt="" width-obs="600" height-obs="361" /> <p class="caption small"><i>The diagram shows a scan and the parts of a scanner. (Also see <SPAN href="#Page_21">page 21</SPAN>.)</i></p> </div>
<div class="pb" id="Page_14">14</div>
<p>In one representative hospital, 17 different kinds of radioisotope
measurements are available to aid physicians in
making their diagnoses. All the methods use tracer quantities
of materials. Other hospitals may use only a few of
them, some may use even
more. In any case they are
merely tools to augment the
doctors’ skill. Examples of
measurements that can be
made include blood volume,
blood circulation rate, red
blood cell turnover, glandular
activity, location of cancerous
tissue, and rates of formation
of bone tissue or blood
cells.</p>
<p>Of the more than 100 different
radioisotopes that have
been used by doctors during
the past 30 years, five have
received by far the greatest
attention. These are iodine-131,
phosphorus-32, gold-198,
chromium-51, and iron-59.
Some others have important
uses, too, but have been less
widely employed than these five. The use of individual radioisotopes
in making important diagnostic tests makes a
fascinating story. Typical instances will be described in
the following pages.</p>
<div class="fig"> id="pic_16"> <ANTIMG src="images/pmg009.jpg" alt="" width-obs="500" height-obs="528" /> <p class="caption small"><i>A differential multi-detector developed at Brookhaven National Laboratory locates brain tumors
with positron-emitting isotopes.
By using many pairs of detection
crystals, the device shortens the
scanning time and increases accuracy.
(See <SPAN href="#cover">cover</SPAN> for another type of positron scanner.)</i></p>
</div>
<h3 id="c10">Arsenic-74</h3>
<p>Brain tumors tend to concentrate certain ions (charged
atoms or molecules). When these ions are gamma-ray
emitters, it is possible to take advantage of the penetrating
power of their gamma rays to locate the tumor with a
scanning device located outside the skull.</p>
<p>Arsenic-74 and copper-64 are isotopes emitting <i>positrons</i>,<SPAN class="fn" id="fr_8" href="#fn_8">[8]</SPAN>
which have one peculiar property. Immediately
after a positron is emitted from a nucleus it decays, producing
two gamma rays that travel in exactly opposite
directions. The scanning device has two detectors called
<span class="pb" id="Page_15">15</span>
scintillation counters, one mounted on each side of the
patient’s head.</p>
<p>The electrical circuitry in the scanner is such that only
those gamma rays are counted that impinge simultaneously
on both counters. This procedure eliminates most of the
“noise”, or scattered and background radiation.</p>
<h3 id="c11">Chromium-51</h3>
<p>Because chromium, in the molecule sodium chromate,
attaches itself to red blood cells, it is useful in several
kinds of tests. The procedures are slightly complicated,
but yield useful information. In one, a sample of the
patient’s blood is withdrawn, stabilized with heparin (to
prevent clotting) and incubated with a tracer of radioactive
sodium chromate. Excess chromate that is not taken up by
the cells is reduced and washed away. Then the radioactivity
of the cells is measured, just before injection into
the patient. After a suitable time to permit thorough mixing
of the added material throughout the blood stream, a new
blood sample is taken and its radioactivity is measured.
The total volume of red blood cells then can be calculated
by dividing the total radioactivity of the injected sample
by the activity per milliliter of the second sample.</p>
<div class="fig"> id="pic_17"> <ANTIMG src="images/pmg009a.jpg" alt="" width-obs="500" height-obs="189" /> <p class="caption small"><i>Spleen scans made with red blood cells, which had been altered by heat treatment and tagged with chromium-51. Such damaged cells are selectively removed by the spleen. A is a normal spleen. B
shows an abscess in the spleen. Note dark ring of radioactivity
surrounding the lighter area of decreased activity at the central
portion of spleen.</i></p>
</div>
<p>In certain types of anemia the patient’s red blood cells
die before completing the usual red-cell lifetime of about
120 days. To diagnose this, red cells are tagged with
chromium-51 (⁵¹Cr) in the manner just described. Then
<span class="pb" id="Page_16">16</span>
some of them are injected back into the patient and an identical
sample is injected into a compatible normal individual.
If the tracer shows that the cells’ survival time is too
short in both recipients to the same degree, the conclusion
is that the red cells themselves must be abnormal. On the
other hand, if the cell-survival time is normal in the normal
individual and too short in the patient, the diagnosis is
that the patient’s blood contains some substance that destroys
the red cells.</p>
<p>When chromium trichloride, CrCl₃, is used as the tagging
agent, the chromium is bound almost exclusively to plasma
proteins, rather than the red cells. Chromium-51 may
thus be used for estimating the volume of plasma circulating
in the heart and blood vessels. The same type of
computation is carried on for red cells (after correction
for a small amount of chromium taken up by the red blood
cells). This procedure is easy to carry out because the
radioactive chromium chloride is injected directly into a
vein.</p>
<p>An ingenious automatic device has been devised for
computing a patient’s total blood volume using the ⁵¹Cr
measurement of the red blood cell volume as its basis.
This determination of total blood volume is of course
necessary in deciding whether blood or plasma transfusions
are needed in cases involving bleeding, burns,
or surgical shock. This ⁵¹Cr procedure was used during
the Korean War to determine how much blood had been
lost by wounded patients, and helped to save many, many
lives.</p>
<p>For several years, iodine-131 has been used as a tracer
in determining cardiac output, which is the rate of blood
flow from the heart. It has appeared recently that red
blood cells tagged with ⁵¹Cr are more satisfactory for this
measurement than iodine-labeled albumin in the blood
serum. It is obvious that the blood-flow rate is an extremely
important physiological quantity, and a doctor must
know it to treat either heart ailments or circulatory disturbances.</p>
<p>In contrast to the iodine-131 procedure, which requires
that an artery be punctured and blood samples be removed
regularly for measurement, chromium labeling merely
<span class="pb" id="Page_17">17</span>
requires that a radiation counter be mounted on the outside
of the chest over the aorta (main artery leaving the heart).
A sample of labeled red blood cells is introduced into a
vein, and the recording device counts the radioactivity
appearing in the aorta as a function of time. Eventually, of
course, the counting rate (the number of radioactive disintegrations
per second) levels off when the indicator sample
has become mixed uniformly in the blood stream. From
the shape of the curve on which the data are recorded
during the measurements taken before that time, the operator
calculates the heart output per second.</p>
<div class="fig"> id="pic_18"> <ANTIMG src="images/pmg010.jpg" alt="" width-obs="500" height-obs="576" /> <p class="caption small"><i>In this cardiac output study a probe is positioned over the heart and the passage
of iodine-131 labeled
human serum albumin
through this area is recorded.</i></p>
</div>
<p>Obstetricians caring for expectant mothers use red cells
tagged with ⁵¹Cr to find the exact location of the placenta.
For example, in the condition known as <i>placenta previa</i>, the
placenta—the organ within the uterus by which nourishment
is transferred from the mother’s blood to that of the
unborn child—may be placed in such a position that fatal
bleeding can occur. A radiation-counting instrument placed
over the lower abdomen gives information about the exact
location of the placenta. If an abnormal situation exists,
the attending physician is then alert and ready to cope with
it. The advantages of chromium over iodine-131, which has
also been used, are that smaller doses are required, and
that there is no transfer of radioactivity to the fetal
circulation.</p>
<div class="pb" id="Page_18">18</div>
<p>Still another common measurement using ⁵¹Cr-labeled red
blood cells is the determination of the amount and location
of bleeding from the gastrointestinal tract (the stomach
and bowels). The amount is found by simple measurement
of chromium in the blood that appears in the stools. To
find the location is slightly more complicated. The intestinal
contents are sampled at different levels through
an inserted tube, and the radiation of the samples determined
separately.</p>
<p>Finally, gastrointestinal loss of protein can be measured
with the aid of ⁵¹Cr-labeled blood serum. The serum is
treated with CrCl₃ and then injected into a vein. In several
very serious ailments there is serious loss of blood protein
through the intestines. In these conditions the ⁵¹Cr
level in the intestinal excretions is high, and this alerts the
doctor to apply remedial measures.</p>
<h3 id="c12">Cobalt-60</h3>
<p>Vitamin B₁₂ is a cobalt compound. Normally the few
milligrams of B₁₂ in the body are stored in the liver and
released to the blood stream as needed. In <i>pernicious
anemia</i>, a potentially fatal but curable disease, the B₁₂
content of the blood falls from the usual level of 300-900
micromicrograms per milliliter (ml) to 0 to 100 micromicrograms
per ml. The administration of massive doses
of B₁₂ is the only known remedy for this condition.</p>
<p>If the B₁₂ is labeled with radioactive cobalt, its passage
into the blood stream may be observed by several different
methods. The simplest is to give the B₁₂ by mouth, and
after about 8 hours study the level of cobalt radioactivity
in the blood. Cobalt-60 has been used for several years,
but recently cobalt-58 has been found more satisfactory.
It has a half-life of 72 days while ⁶⁰Co has a 5.3-year half-life.
This reduces greatly the amount of radiation to the
patient’s liver by the retained radioactivity.</p>
<h3 id="c13">Iodine-131</h3>
<p>Like chromium-51, iodine is a versatile tracer element.
It is used to determine blood volume, cardiac output,
plasma volume, liver activity, fat metabolism, thyroid
<span class="pb" id="Page_19">19</span>
cancer metastases, brain tumors, and the size, shape, and
activity of the thyroid gland.</p>
<div class="fig"> id="pic_19"> <ANTIMG src="images/pmg011.jpg" alt="" width-obs="500" height-obs="105" /> <p class="caption small"><i>A linear photoscanner produced these pictures of (A) a normal thyroid, (B) an enlarged thyroid, and (C) a cancerous thyroid.</i></p> </div>
<p>Because of its unique connection with the thyroid gland,
iodine-131 is most valuable in measurements connected
with that organ. Thyroxin, an iodine compound, is manufactured
in the thyroid gland, and transferred by the blood
stream to the body tissues. The thyroxin helps to govern
the oxygen consumption of the body and therefore helps
control its metabolism. Proper production of thyroxin is
essential to the proper utilization of nutrients. Lowered
metabolism means increased body weight. Lowered thyroid
activity may mean expansion of the gland, causing one
form of goiter.</p>
<p>Iodine-131 behaves in the body just as the natural non-radioactive
isotope, iodine-127, does, but the radioactivity
permits observation from outside the body with some form
of radiation counter. Iodine can exist in the body in many
different chemical compounds, and the counter can tell
where it is but not in what form. Hence chemical manipulation
is necessary in applying this technique to different
diagnostic procedures.</p>
<p>The thyroid gland, which is located at the base of the
neck, is very efficient in trapping inorganic iodide from
the blood stream, concentrating and storing the iodine-containing
material and gradually releasing it to the blood
stream in the form of protein-bound iodine (PBI).</p>
<p>One of the common diagnostic procedures for determining
thyroid function, therefore, is to measure the percentage
of an administered dose of ¹³¹I that is taken up by the
gland. Usually the patient is given a very small dose of
radioactive sodium iodide solution to drink, and two hours
later the amount of iodine in the gland is determined by
measuring the radiation coming from the neck area. In
<span class="pb" id="Page_20">20</span>
hyperthyroidism, or high thyroid gland activity, the gland
removes iodide ions from the blood stream more rapidly
than normal.</p>
<div class="fig"> id="pic_20"> <ANTIMG src="images/pmg012.jpg" alt="" width-obs="600" height-obs="231" /> <p class="caption small"><b>Screening test for Hyperthyroidism</b></p> </div>
<div class="fig"> id="pic_21"> <ANTIMG src="images/pmg012a.jpg" alt="" width-obs="600" height-obs="313" /> <p class="caption small"><i>It is especially important in isotope studies on infants and small children that the radiation exposure be low. By carrying out studies in the whole body counter room, the administered dose can be
greatly reduced. The photographs illustrate a technique of measuring
radioiodine uptake in the thyroid gland with extremely small
amounts of a mixture of iodine-131 and iodine-125. A shows a
small television set that is mounted above the crystal in such a
way that good viewing requires that the head be kept in the desired
position. This helps solve the problem of keeping small children
still during a 15-minute counting period. B shows a child in position
for a thyroid uptake study.</i></p>
</div>
<p>This simple procedure has been used widely. One difficulty
in using it is that its success is dependent upon the
time interval between injection and measurement. An
overactive gland both concentrates iodine rapidly and also
<span class="pb" id="Page_21">21</span>
discharges it back to the blood stream as PBI more
rapidly than normal. Modifications of the test have been
made to compare the amount of iodine-131 that was administered
with the amount circulating in the blood as PBI.
The system acquires chemical separation of the two forms
of iodine from a sample of blood removed from a vein,
followed by separate counting. This computation of the
“conversion ratio” of radioactive plasma PBI to plasma-total
¹³¹I gives results that are less subject to misinterpretation.</p>
<p>To determine local activity in small portions of the
thyroid, an automatic scanner is used. A collimator<SPAN class="fn" id="fr_9" href="#fn_9">[9]</SPAN>
shields the detector (a Geiger-Müller tube or scintillating
crystal) so that only those impulses originating within a
very small area are accepted by the instrument. The detector
is then moved back and forth slowly over the entire
area and the radiation is automatically recorded at definite
intervals, creating a “map” of the active area. In cases
where lumps, or nodules, have been discovered in the thyroid,
the map is quite helpful in distinguishing between
cancerous and benign nodules. The former
are almost always less radioactive than
surrounding tissues.</p>
<div class="fig"> id="pic_22"> <ANTIMG src="images/pmg012c.jpg" alt="" width-obs="268" height-obs="601" /> <p class="caption small"><i>Seven serial scans made with the whole body scanner were put together to provide a whole body scan of this patient with thyroid cancer that
had spread to the lung. One millicurie of
iodine-131 was administered and the scan made
72 hours later. Note the uptake in the lung. This
patient was successfully treated with large
doses of iodine-131.</i></p>
</div>
<p>Fragments of cancerous thyroid tissue
may migrate to other parts of the body and
grow there. These new cancers are known
as metastatic cancers and are a signal
of an advanced state of disease. In such a
situation even complete surgical removal
of the original cancer may not save the
patient. If these metastases are capable of concentrating
iodine (less than 10% of them are), they can be located by
scanning the whole body in the manner that was just described.
When a thyroid cancer is discovered, therefore,
a doctor may look for metastases before deciding to
operate.</p>
<div class="pb" id="Page_22">22</div>
<p>Human blood serum albumin labeled with ¹³¹I is used for
measurement of the volume of circulating plasma. The
procedure is quite similar to that used with radioactive
chromium. Iodinated human serum albumin labeled with
¹³¹I is injected into a vein. Then, after allowing time for
complete mixing of the sample with the blood, a second
sample is counted using a scintillation counter.</p>
<div class="fig"> id="pic_23"> <ANTIMG src="images/pmg013.jpg" alt="" width-obs="121" height-obs="802" /> <p class="caption small"><i>Time-lapse motion pictures of the liver of a 3-year-old girl were made with the scintillation camera 1 hour after injection of 50 microcuries of iodine-131-labeled rose bengal dye. This
child was born without a bile-duct system and an artificial bile
duct had been created surgically. She developed symptoms that
caused concern that the duct had closed. These scans show the
mass of material containing the radioactive material (small
light area) moving downward and to the right, indicating that
the duct was still open.</i></p>
</div>
<p>For many years, a dye known as <i>rose bengal</i> has been
used in testing liver function. About 10 years ago this
procedure was improved by labeling the dye with ¹³¹I. When
this dye is injected into a vein it goes to the liver, which
removes it from the blood stream and transfers it to the
intestines to be excreted. The rate of disappearance of the
dye from the blood stream is therefore a measure of the
liver activity. Immediately after administration of the
radioactive dye, counts are recorded, preferably continuously
from several sites with shielded, collimated detectors.
One counter is placed over the side of the head or
the thigh to record the clearance of the dye from the blood
stream. A second is placed over the liver, and a third over
the abdomen to record the passage of the dye into the small
intestine.</p>
<p>Human serum albumin labeled with ¹³¹I is sometimes
used for location of brain tumors. It appears that tumors
<span class="pb" id="Page_23">23</span>
alter a normal “barrier” between the brain and blood in
such a manner that the labeled albumin can penetrate
tumorous tissues although it would be excluded from healthy
brain tissue.</p>
<div class="fig"> id="pic_24"> <ANTIMG src="images/pmg013a.jpg" alt="Showing:" width-obs="500" height-obs="291" /></div>
<p>The brain behaves almost uniquely among body tissues in
that a “blood-brain barrier” exists, so that substances
injected into the blood stream will not pass into brain
cells although they will pass readily into muscular tissue.
This blood-brain barrier does not exist in brain tumors. A
systematic scanning of the skull then permits location of
these cancerous “hot spots”.</p>
<h3 id="c14">Iron-59</h3>
<p>Iron is a necessary constituent of red blood cells, so its
radioactive form, ⁵⁹Fe, has been used frequently in measurement
of the rate of formation of red cells, the lifetime
of red cells, and red cell volumes. The labeling is
more difficult than labeling with chromium for the same
purposes, so this procedure no longer has the importance
it once had.</p>
<p>On the other hand, direct measurement of absorption of
iron by the digestive tract can be accomplished only by
using ⁵⁹Fe. In <i>achlorhydria</i> the gastric juice in the stomach
is deficient in hydrochloric acid, and this condition has
been shown to lower the iron absorption. A normal diet
contains much more iron than the body needs, but in special
<span class="pb" id="Page_24">24</span>
cases, sometimes called “tired blood” in advertising for
medicines, iron compounds are prescribed for the patient.
If ⁵⁹Fe is included, its appearance in the blood stream can
be monitored and the effectiveness of the medication noted.</p>
<div class="fig"> id="pic_25"> <ANTIMG src="images/pmg014.jpg" alt="" width-obs="600" height-obs="471" /> <p class="caption small"><i>This multiple-port scintillation counter is used for iron-kinetic studies. The tracer dose of iron-59 is administered into the arm vein and then the activities in the bone marrow, liver, and spleen
are recorded simultaneously with counters positioned over these
areas, and show distribution of iron-59 as a function of time. When
the data are analyzed in conjunction with iron-59 content in blood,
information can be obtained about sites of red blood cell production
and destruction.</i></p>
</div>
<h3 id="c15">Phosphorus-32</h3>
<p>The phosphate ion is a normal constituent of the blood.
In many kinds of tumors, phosphates seem to be present
in the cancerous tissue in a concentration several times
that of the surrounding healthy tissue. This offers a way
of using phosphorus-32 to distinguish between cancer cells
and their neighbors. Due to the fact that ³²P gives off beta
rays but no gammas, the counter must be placed very close
to the suspected tissue, since beta particles have very
<span class="pb" id="Page_25">25</span>
little penetrating power. This fact limits the use of the
test to skin cancers or to cancers exposed by surgery.</p>
<p>Some kinds of brain tumors, for instance, are difficult
to distinguish visually from the healthy brain tissue. In such
cases, the patient may be given ³²P labeled phosphate
intravenously some hours before surgery. A tiny beta-sensitive
probe counter then can be moved about within
the operative site to indicate to the surgeon the limits of
the cancerous area.</p>
<h3 id="c16">Sodium-24</h3>
<p>Normal blood is about 1% sodium chloride or ordinary
salt. This fact makes possible the use of ²⁴Na in some
measurements of the blood and other fluids. The figure
illustrates this technique. A sample of ²⁴NaCl solution is
injected into a vein in an arm or leg. The time the radioisotope
arrives at another part of the body is detected with
a shielded radiation counter. The elapsed time is a good
indication of the presence or absence of constrictions or
obstructions in the circulatory system.</p>
<div class="fig"> id="pic_26"> <ANTIMG src="images/pmg014a.jpg" alt="Showing" width-obs="600" height-obs="377" /></div>
<p>The passage of blood through the heart may also be
measured with the aid of sodium-24. Since this isotope
emits gamma rays, measurement is done using counters
on the outside of the body, placed at appropriate locations
above the different sections of the heart.</p>
<div class="pb" id="Page_26">26</div>
<div class="fig"> id="pic_27"> <ANTIMG src="images/pmg015.jpg" alt="Showing:" width-obs="600" height-obs="462" /></div>
<h3 id="c17">Technetium-99<sup>m</sup></h3>
<p>Because of its short half-life of six hours, technetium-99<sup>m</sup><SPAN class="fn" id="fr_10" href="#fn_10">[10]</SPAN>
is coming into use for diagnosis using scanning devices,
particularly for brain tumors. It lasts such a short
time it obviously cannot be kept in stock, so it is prepared
by the beta decay of molybdenum-99.<SPAN class="fn" id="fr_11" href="#fn_11">[11]</SPAN> A stock of molybdenum
is kept in a shielded container in which it undergoes
radioactive decay yielding technetium. Every morning, as
the technetium is needed, it is extracted from its parent
by a brine solution. This general procedure of extracting
a short-lived isotope from its parent is also used in other
cases. We shall see later that radon gas is obtained by an
analogous method from its parent, radium.</p>
<div class="pb" id="Page_27">27</div>
<div class="fig"> id="pic_28"> <ANTIMG src="images/pmg015a.jpg" alt="" width-obs="600" height-obs="740" /> <p class="caption small"><i>Using a “nuclear cow” to get technetium from its parent isotope. The “cow” is being
fed saltwater through a tube.
The saltwater drains through
a high-radiation (hot) isotope.
The resultant drip-off is a
daughter such as technetium-99<sup>m</sup>.
This new, mild isotope
can be mixed with other elements
and these become the
day’s supply of radioisotopes
for other scans. Technetium-99<sup>m</sup>
decays in 6 hours. Thus
greater amounts, with less
possibility of injury, can be
administered and a better
picture results.</i></p>
</div>
<h3 id="c18">Thulium-170 and Gamma Radiography</h3>
<p>For years it has been recognized that there would be
many uses for a truly portable device for taking X-ray
pictures—one that could be carried by the doctor to the
bedside or to the scene of an accident. Conventional X-ray
equipment has been in use by doctors for many years, and
highly efficient apparatus has become indispensable, especially
in treating bone conditions. There is, however, a
need for a means of examining patients who cannot be
moved to a hospital X-ray room, and are located where
electric current sources are not available.</p>
<p>A few years ago, a unit was devised that weighed only a
few pounds, and could take “X-ray pictures” (actually
gamma radiographs) using the gamma rays from the radioisotope
thulium-170. The thulium source is kept inside a
lead shield, but a photographic shutter-release cable can
be pressed to move it momentarily over an open port in
the shielding. The picture is taken with an exposure of a
few seconds. A somewhat similar device uses strontium-90
as the source of beta radiation that in turn stimulates
the emission of gamma rays from a target within the
instrument.</p>
<div class="pb" id="Page_28">28</div>
<div class="fig"> id="pic_29"> <ANTIMG src="images/pmg016.jpg" alt="" width-obs="500" height-obs="629" /> <p class="caption small"><i>A technician holds an inexpensive portable X-ray unit that was developed by the Argonne National Laboratory. Compare
its size with the standard X-ray machine
shown at left and above.</i></p>
</div>
<p>Still more recently, ¹²⁵I has been used very successfully
in a portable device as a low-energy gamma source for
radiography. The gamma rays from this source are sufficiently
penetrating for photographing the arms and legs,
and the necessary shielding is easily supplied to protect
the operator. By contrast with larger devices, the gamma-ray
source can be as small as one-tenth millimeter in
diameter, virtually a point source; this makes possible
maximum sharpness of image. The latest device, using up
to one curie<SPAN class="fn" id="fr_12" href="#fn_12">[12]</SPAN> of ¹²⁵I, weighs 2 pounds, yet has adequate
shielding for the operator. It is truly portable.</p>
<p>If this X-ray source is combined with a rapid developing
photographic film, a physician can be completely freed
from dependence upon the hospital laboratory for emergency
X rays. A finished print can be ready for inspection in
10 seconds. The doctor thus can decide quickly whether
it is safe to move an accident victim, for instance. In
military operations, similarly, it becomes a simple matter
to examine wounded soldiers in the field where conventional
equipment is not available.</p>
<h3 id="c19">Tritium</h3>
<p>More than 30 years ago, when deuterium (heavy hydrogen)
was first discovered, heavy water (D₂O) was used for the
<span class="pb" id="Page_29">29</span>
determination of total body water. A small sample of
heavy water was given either intravenously or orally, and
time was allowed for it to mix uniformly with all the water
in the body (about 4 to 6 hours). A sample was then obtained
of the mixed water and analyzed for its heavy water
content. This procedure was useful but it was hard to make
an accurate analysis of low concentrations of heavy water.</p>
<p>More recently, however, tritium (³H) (radioactive hydrogen)
has been produced in abundance. Its oxide, tritiated
water (³H₂O), is chemically almost the same as ordinary
water, but physically it may be distinguished by the beta
rays given off by the tritium. This very soft (low-energy)
beta ray requires the use of special counting equipment,
either a windowless flow-gas counter or a liquid scintillator,
but with the proper techniques accurate measurement
is possible. The total body water can then be computed by
the general isotope dilution formula used for measuring
blood plasma volume.</p>
<div class="fig"> id="pic_30"> <ANTIMG src="images/pmg016a.jpg" alt="" width-obs="600" height-obs="454" /> <p class="caption small"><i>The total body water is determined by the dilution method using tritiated water. This technician is purifying a urine sample so that the tritium content can be determined and the total body water
calculated.</i></p>
</div>
<div class="pb" id="Page_30">30</div>
<h3 id="c20">Activation Analysis</h3>
<p>Another booklet in this series,
<i>Neutron Activation Analysis</i>,
discusses a new process by which microscopic quantities
of many different materials may be analyzed accurately.
Neutron irradiation of these samples changes some
of their atoms to radioactive isotopes. A multichannel
analyzer instrument gives a record of the concentration of
any of about 50 of the known elements.</p>
<p>One use of this technique involved the analysis of a hair
from Napoleon’s head. More than 100 years after his death
it was shown that the French Emperor had been given
arsenic in large quantities and that this possibly caused
his death.</p>
<p>The ways in which activation analysis can be applied to
medical diagnosis are at present largely limited to toxicology,
the study of poisons, but the future may bring new
possibilities.</p>
<p>Knowledge is still being sought, for example, about the
physiological role played by minute quantities of some of
the elements found in the body. The ability to determine
accurately a few parts per million of “trace elements” in
the various tissues and body fluids is expected to provide
much useful information as to the functions of these
materials.</p>
<h3 id="c21">Summary</h3>
<p>A large number of different radioisotopes have been
used for measurement of disease conditions in the human
body. They may measure liquid volumes, rates of flow or
rates of transfer through organs or membranes; they may
show the behavior of internal organs; they may differentiate
between normal and malignant tissues. Hundreds of hospitals
are now making thousands of these tests annually.</p>
<p>This does not mean that all the diagnostic problems have
been solved. Much of the work is on an experimental rather
than a routine basis. Improvements in techniques are still
being made. As quantities of radioisotopes available for
these purposes grow, and as the cost continues to drop, it
is expected there will be still more applications. Finally,
this does not mean we no longer need the doctor’s diagnostic
<span class="pb" id="Page_31">31</span>
skill. All radioisotope procedures are merely tools
to aid the skilled physician. As the practice of medicine
has changed from an art to a science, radioisotopes have
played a useful part.</p>
<h2 id="c22">THERAPY</h2>
<h3 id="c23">A Successful Case</h3>
<p>A doctor recently told this story about a cancer patient
who was cured by irradiation with cobalt-60.</p>
<p>“A 75-year-old white male patient, who had been hoarse
for one month, was treated unsuccessfully with the usual
medications given for a bad cold. Finally, examination of
his larynx revealed an ulcerated swelling on the right
vocal cord. A biopsy (microscopic examination of a tissue
sample) was made, and it was found the swelling was a
squamous-cell cancer.</p>
<p>“Daily radiation treatment using a cobalt-60 device was
started and continued for 31 days. This was in September
1959. The cobalt-60 unit is one that can be operated by
remote control. It positions radioactive cobalt over a
collimator, which determines the size of the radiation beam
reaching the patient. The machine may be made to rotate
around the patient or can be used at any desired angle or
position.</p>
<div class="fig"> id="pic_31"> <ANTIMG src="images/pmg017.jpg" alt="Showing:" width-obs="500" height-obs="252" /></div>
<div class="pb" id="Page_32">32</div>
<p>“When the treatment series was in progress, the patient’s
voice was temporarily made worse, but it returned to
normal within two months after the treatment ended. The
radiation destroyed the cancerous growth, and frequent
examinations over 6 years since have failed to reveal any
regrowth.</p>
<p>“The treatment spared the patient’s vocal cords, and his
voice, airway, and food passage were preserved.”</p>
<p>This dramatic tale with a happy ending is a good one
with which to start a discussion of how doctors use radioisotopes
for treatment of disease.</p>
<h3 id="c24">General Principles</h3>
<p>Radioisotopes have an important role in the treatment
of disease, particularly cancer. It is still believed that
cancer is not one but several diseases with possible multiple
causes. Great progress is being made in development
of chemicals for relief of cancer. Nevertheless, radiation
and surgery are still the main methods for treating cancer,
and there are many conditions in which relief can be obtained
through use of radiation. Moreover, the imaginative
use of radioisotopes gives much greater flexibility in radiation
therapy. This is expected to be true for some years
to come even as progress continues.</p>
<p>Radioisotopes serve as concentrated sources of radiation
and frequently are localized within the diseased cells or
organs. The dose can be computed to yield the maximum
therapeutic effect without harming adjacent healthy tissues.
Let us see some of the ways in which this is done.</p>
<h3 id="c25">Iodine-131 and Iodine-132</h3>
<p>Iodine, as was mentioned earlier, concentrates in the
thyroid gland, and is converted there to protein-bound
iodine that is slowly released to the blood stream. Iodine-131,
in concentrations much higher than those used in
diagnostic tests, will irradiate thyroid cells, thereby
damage them, and reduce the activity of an overactive
thyroid (hyperthyroidism). The energy is released within
the affected gland, and much of it is absorbed there.
Iodine-131 has a half-life of 8.1 days. In contrast, ¹³²I has
<span class="pb" id="Page_33">33</span>
a half-life of only 2.33 hours. What this means is that the
same weight of radioactive ¹³²I will give a greater radiation
dose than ¹³¹I would, and lose its activity rapidly enough to
present much less hazard by the time the iodine is released
to the blood stream. Iodine-132 is therefore often
preferred for treatment of this sort.</p>
<h3 id="c26">Boron-10</h3>
<p>Boron-10 has been used experimentally in the treatment
of inoperable brain tumors. <i>Glioblastoma multiforme</i>, a
particularly malignant form of cancer, is an invariably
fatal disease in which the patient has a probable life expectancy
of only 1 year. The tumor extends roots into
normal tissues to such an extent that it is virtually impossible
for the surgeon to remove all malignant tissue
even if he removes enough normal brain to affect the functioning
of the patient seriously. With or without operation
the patient dies within months. This is therefore a case in
which any improvement at all is significantly helpful.</p>
<p>The blood-brain barrier that was mentioned earlier
minimizes the passages of many materials into normal
brain tissues. But when some organic or inorganic compounds,
such as the boron compounds, are injected into
the blood stream, they will pass readily into brain tumors
and <i>not</i> move into normal brain cells.</p>
<p>Boron-10 absorbs slow neutrons readily, and becomes
boron-11, which disintegrates almost immediately into
alpha particles and a lithium isotope. Alpha particles,
remember, have very little penetrating power, so all the
energy of the alpha radioactivity is expended within the
individual tumor cells. This is an ideal situation, for it
makes possible destruction of tumor cells with virtually
no harm to normal cells, even when the two kinds are
closely intermingled.</p>
<p>Slow neutrons pass through the human body with very
little damage, so a fairly strong dose of them can be safely
applied to the head. Many of them will be absorbed by the
boron-10, and maximum destruction of the cancer will
occur, along with minimum hazard to the patient. This
treatment is accomplished by placing the head of the patient
in a beam of slow neutrons emerging from a nuclear reactor
a few minutes after the boron-10 compound has been
injected into a vein.</p>
<div class="pb" id="Page_34">34</div>
<div class="fig"> id="pic_32"> <ANTIMG src="images/pmg018.jpg" alt="" width-obs="500" height-obs="468" /> <p class="caption small"><b>SEQUENCE OF EVENTS IN NEUTRON CAPTURE THERAPY USING BORON-10</b></p> <p class="caption small"><i>Neutron capture treatment of a brain tumor, using the Brookhaven National Laboratory research reactor (center).</i></p>
</div>
<div class="fig"> id="pic_33"> <ANTIMG src="images/pmg018a.jpg" alt="" width-obs="247" height-obs="285" /> <p class="caption small"><i>(1) A lead shutter shields the patient from reactor neutrons.</i></p> </div>
<div class="fig"> id="pic_34"> <ANTIMG src="images/pmg018a2.jpg" alt="" width-obs="249" height-obs="282" /> <p class="caption small"><i>(2) A compound containing the stable element boron is injected into the bloodstream; the tumor absorbs most of the boron.</i></p>
</div>
<div class="fig"> id="pic_35"> <ANTIMG src="images/pmg018a3.jpg" alt="" width-obs="233" height-obs="280" /> <p class="caption small"><i>(3) After 8 minutes, when the tumor is saturated, the shutter is removed and neutrons bombard the brain, splitting boron atoms so that fragments destroy tumor tissue.</i></p>
</div>
<div class="fig"> id="pic_36"> <ANTIMG src="images/pmg018a4.jpg" alt="" width-obs="231" height-obs="288" /> <p class="caption small"><i>(4) Twenty minutes later the shutter is closed and the treatment ends.</i></p> </div>
<div class="pb" id="Page_35">35</div>
<p>The difficulty is that most boron compounds themselves
are poisonous to human tissues, and only small concentrations
can be tolerated in the blood. Efforts have been
made, with some success, to synthesize new boron compounds
that have the greatest possible degree of selective
absorption by the tumors. Both organic and inorganic
compounds have been tried, and the degree of selectivity
has been shown to be much greater for some than for
others. So far it is too early to say that any cures have
been brought about, but results have been very encouraging.
The ideal drug, one which will make possible complete
destruction of the cancer without harming the patient, is
probably still to be devised.</p>
<h3 id="c27">Phosphorus-32</h3>
<p>Another disease which is peculiarly open to attack by
radioisotopes is <i>polycythemia vera</i>. This is an insidious
ailment of a chronic, slowly progressive nature, characterized
by an abnormal increase in the number of red
blood cells, an increase in total blood volume, enlargement
of the spleen, and a tendency for bleeding to occur.
There is some indication that it may be related to leukemia.</p>
<p>Until recent years there was no very satisfactory treatment
of this malady. The ancient practice of bleeding was
as useful as anything, giving temporary relief but not
striking at the underlying cause. There is still no true
cure, but the use of phosphorus-32 has been very effective
in causing disappearance of symptoms for periods from
months to years, lengthening the patient’s life considerably.
The purpose of the ³²P treatment (using a sodium-radiophosphate
solution) is not to destroy the excess of red
cells, as had been tried with some drugs, but rather to
slow down their formation and thereby get at the basic
cause.</p>
<p>Phosphorus-32 emits pure beta rays having an average
path in tissue only 2 millimeters long. Its half-life is
14.3 days. When it is given intravenously it mixes rapidly
with the circulating blood and slowly accumulates in tissues
that utilize phosphates in their metabolism. This brings
<span class="pb" id="Page_36">36</span>
appreciable concentration in the blood-forming tissues
(about twice as much in blood cells as in general body cells).</p>
<div class="fig"> id="pic_37"> <ANTIMG src="images/pmg019.jpg" alt="Showing:" width-obs="500" height-obs="213" /></div>
<div class="fig"> id="pic_38"> <ANTIMG src="images/pmg019a.jpg" alt="" width-obs="500" height-obs="406" /> <p class="caption small"><i>Survival of</i> polycythemia vera <i>patients after ³²P therapy</i>.</p> </div>
<p>One other pertinent fact is that these rapidly dividing
hematopoietic cells are extremely sensitive to radiation.
(Hematopoietic cells are those that are actively forming
blood cells and are therefore those that should be attacked
selectively.) The dose required is of course many times
that needed for diagnostic studies, and careful observation
of the results is necessary to determine that exactly the
desired effect has been obtained.</p>
<p>There exists some controversy over this course of
treatment. No one denies that the lives of patients have
been lengthened notably. Nevertheless since the purpose
of the procedure is to reduce red cell formation, there
exists the hazard of too great a reduction, and the possibility
of causing leukemia (a disease of too few red cells). There
<span class="pb" id="Page_37">37</span>
may be a small increase in the number of cases of leukemia
among those treated with ³²P compared with the general
population. The controversy arises over whether the ³²P
treatment <i>caused</i> the leukemia, or whether it merely prolonged
the lives of the patients until leukemia appeared
as it would have in these persons even without treatment.
This is probably quibbling, and many doctors believe that
the slight unproven risk is worth taking to produce the
admitted lengthy freedom from symptoms.</p>
<h3 id="c28">Gold-198</h3>
<p>The last ailment we shall discuss in this section is the
accumulation of large quantities of excess fluid in the
chest and abdominal cavities from their linings, as a
consequence of the growth of certain types of malignant
tumors.</p>
<p>Frequent surgical drainage was at one time the only
very useful treatment, and of course this was both uncomfortable
and dangerous. The use of radioactive colloidal
suspensions, primarily colloidal gold-198, has been quite
successful in palliative treatment: It does not cure, but it
does give marked relief.</p>
<div class="fig"> id="pic_39"> <ANTIMG src="images/pmg019b.jpg" alt="Showing:" width-obs="500" height-obs="410" /></div>
<p>Radioactive colloids (a colloid is a suspension of one
very finely divided substance in some other medium) can
be introduced into the abdominal cavity, where they may
<span class="pb" id="Page_38">38</span>
remain suspended or settle out upon the lining. In either
case, since they are not dissolved, they do not pass
through the membranes or cell walls but remain within the
cavity. Through its destructive and retarding effect on the
cancer cells the radiation inhibits the oozing of fluids.</p>
<p>Gold-198 offers several advantages in such cases. It has
a short half-life (2.7 days); it is chemically inert and
therefore nontoxic; and it emits beta and gamma radiation
that is almost entirely absorbed by the tissues in its immediate
neighborhood.</p>
<p>The results have been very encouraging. There is admittedly
no evidence of any cures, or even lengthening
of life, but there has been marked reduction of discomfort
and control of the oozing in over two-thirds of the cases
treated.</p>
<h3 id="c29">Beads, Needles, and Applicators</h3>
<p>Radium salts were the first materials to be used for
radiation treatment of cancer. Being both very expensive
and very long-lived, they could not be injected but were
used in temporary implants. Radium salts in powder form
were packed into tiny hollow needles about 1 centimeter
long, which were then sealed tightly to prevent the escape
of radon gas. As radium decays (half-life 1620 years) it
becomes gaseous radon. The latter is also radioactive, so
it must be prevented from escaping. These gold needles
could be inserted into tumors and left there until the desired
dosage had been administered. One difficulty in
radium treatment was that the needles were so tiny that
on numerous occasions they were lost, having been thrown
out with the dressings. Then, both because of their value
and their hazard, a frantic search ensued when this happened,
not always ending successfully.</p>
<div class="pb" id="Page_39">39</div>
<div class="fig"> id="pic_40"> <ANTIMG src="images/pmg020.jpg" alt="" width-obs="500" height-obs="782" /> <p class="caption small"><i>The needle used for implantation of yttrium-90 pellets into the pituitary gland is shown in the top photograph. In the center X ray the needle is in place and the pellets have just been passed through
it into the bone area surrounding the pituitary gland. The bottom
X ray shows the needle withdrawn and the pellets within the bone.</i></p>
</div>
<div class="pb" id="Page_40">40</div>
<p>The fact that radon, the daughter of radium, is constantly
produced from its parent, helped to eliminate some of this
difficulty. Radium could be kept in solution, decaying constantly
to yield radon. The latter, with a half-life of 4 days,
could be sealed into gold seeds 3 by 0.5 millimeters and
left in the patient without much risk, even if he failed to
return for its removal at exactly the appointed time. The
cost was low even if the seeds were lost.</p>
<p>During the last 20 years, other highly radioactive sources
have been developed that have been used successfully.
Cobalt-60 is one popular material. Cobalt-59 can be
neutron-irradiated in a reactor to yield cobalt-60 with
such a high specific activity that a small cylinder of it is
more radioactive than the entire world’s supply of radium.
Cobalt-60 has been encapsulated in gold or silver needles,
sometimes of special shapes for adaptation to specific
tumors such as carcinoma of the cervix. Sometimes needles
have been spaced at intervals on plastic ribbon that adapts
itself readily to the shape of the organ treated.</p>
<p>Gold-198 is also an interesting isotope. Since it is
chemically inert in the body, it needs no protective coating,
and as is the case with radon, its short half-life makes its
use simpler in that the time of removal is not of critical
importance.</p>
<p>Ceramic beads made of yttrium-90 oxide are a moderately
new development. One very successful application of
this material has been for the destruction of the pituitary
gland.</p>
<p>Cancer may be described as the runaway growth of cells.
The secretions of the pituitary gland serve to stimulate
cell reproduction, so it was reasoned that destruction of
this gland might well slow down growth of a tumor elsewhere
in the body. The trouble was that the pituitary is
small and located at the base of the brain. Surgical removal
had brought dramatic relief (not cure) to many
patients, but the surgery itself was difficult and hazardous.
Tiny yttrium-90 oxide beads, glasslike in nature, can
be implanted directly in the gland with much less difficulty
and risk, and do the work of destroying the gland with little
damage to its surroundings. The key to the success of
yttrium-90 is the fact that it is a beta-emitter, and beta
rays have so little penetrating power that their effect is
limited to the immediate area of the implant.</p>
<div class="pb" id="Page_41">41</div>
<h3 id="c30">Teletherapy</h3>
<p>Over 200 teletherapy units are now in use in the United
States for treatment of patients by using very high intensity
sources of cobalt-60 (usually) or cesium-137. Units carrying
sources with intensities of more than a thousand curies
are common.</p>
<div class="fig"> id="pic_41"> <ANTIMG src="images/pmg021.jpg" alt="" width-obs="500" height-obs="424" /> <p class="caption small"><i>The cobalt-60 unit at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, employs a 3000-curie source. This unit has a mechanism that allows for rotation therapy about a stationary
patient. Many different treatment positions are possible. This
patient, shown in position for therapy, has above her chest an
auxiliary diaphragm that consists of an expanded metal tray on
which blocks of either tungsten or lead are placed to absorb
gamma rays and thus shape the field of treatment. In this case
they allow for irradiation of the portions of the neck and chest
delineated by the lines visible on the patient.</i></p>
</div>
<p>Since a curie is the amount of radioactivity in a gram of
radium that is in equilibrium with its decay products, a
1000-curie source is comparable to 2 pounds of pure
radium. Neglecting for the moment the scarcity and enormous
cost of that much radium (millions of dollars), we
<span class="pb" id="Page_42">42</span>
have to consider that it would be large in volume and consequently
difficult to apply. Radiation from such a quantity
cannot be focussed; consequently, either much of it will
fall upon healthy tissue surrounding the cancer or much of
it will be wasted if a narrow passage through the shield is
aimed at the tumor. In contrast, a tiny cobalt source provides
just as much radiation and more if it can be brought
to bear upon the exact spot to be treated.</p>
<div class="fig"> id="pic_42"> <ANTIMG src="images/pmg022.jpg" alt="Diagram of teletherapy unit" width-obs="500" height-obs="478" /></div>
<p>Most interesting of all is the principle by which internal
cancers can be treated with a minimum of damage to the
skin. Deep x-irradiation has always been the approved
treatment for deep-lying cancers, but until recently this
required very cumbersome units. With the modern rotational
device shown in the diagram, a very narrow beam
is aimed at the patient while the source is mounted upon
a carrier that revolves completely around him. The patient
is positioned carefully so that the lesion to be treated is
exactly at the center of the circular path of the carrier.
The result is that the beam strikes its internal target during
the entire circular orbit, but the same amount of radiation
is spread out over a belt of skin and tissue all the
way around the patient. The damage to any one skin cell is
minimized. The advantage of this device over an earlier
device, in which the patient was revolved in a stationary
beam, is that the mechanical equipment is much simpler.</p>
<div class="pb" id="Page_43">43</div>
<h2 id="c31">CONCLUSIONS</h2>
<p>In summary, then, we may say that radioisotopes play
an important role in medicine. For the diagnostician, small
harmless quantities of many isotopes serve as tools to aid
him in gaining information about normal and abnormal life
processes. The usefulness of this information depends upon
his ingenuity in devising questions to be answered, apparatus
to measure the results, and explanations for the results.</p>
<p>For therapeutic uses, on the other hand, the important
thing to remember is that radiation damages many kinds of
cells, especially while they are in the process of division
(reproduction).<SPAN class="fn" id="fr_13" href="#fn_13">[13]</SPAN> Cancer cells are self-reproducing cells,
but do so in an uncontrolled manner. Hence cancer cells
are particularly vulnerable to radiation. This treatment requires
potent sources and correspondingly increases the
hazards of use.</p>
<p>In all cases, the use of these potentially hazardous materials
belongs under the supervision of the U. S. Atomic
Energy Commission.<SPAN class="fn" id="fr_14" href="#fn_14">[14]</SPAN> Licenses are issued by the Commission
after investigation of the training, ability, and facilities
possessed by prospective users of dangerous quantities.
At regular intervals courses are given to train
individuals in the techniques necessary for safe handling,
and graduates of these courses are now located in laboratories
all over the country.</p>
<p>The future of this field cannot be predicted with certainty.
Research in hundreds of laboratories is continuing to add
to our knowledge, through new apparatus, new techniques,
and new experiments. Necessarily the number of totally new
fields is becoming smaller, but most certainly the number
of cases using procedures already established is bound to
increase. We foresee steady improvement and growth in
all uses of radioisotopes in medicine.</p>
<div class="pb" id="Page_44">44</div>
<h2 id="c32">APPENDIX</h2>
<h3>Measuring Instruments<SPAN class="fn" id="fr_15" href="#fn_15">[15]</SPAN></h3>
<p>The measurement of radioactivity must be accomplished
indirectly, so use is made of the physical, chemical, and
electrical effects of radiation on materials. One commonly
used effect is that of ionization. Alpha and beta particles
ionize gases through which they pass, thereby making the
gases electrically conductive. A family of counters uses
this principle: the ionization chamber, the proportional
counter, and the Geiger-Müller counter.</p>
<p>Certain crystals, sodium iodide being an excellent example,
emit flashes of visible light when struck by ionizing
radiation. These crystals are used in scintillation counters.</p>
<h3>Ionization Chambers</h3>
<p>One of a pair of electrodes is a wire located centrally
within a cylinder. The other electrode is the wall of the
chamber. Radiation ionizes the gas within the chamber,
permitting the passage of current between the electrodes.
The thickness of a window in the chamber wall determines
the type of radiation it can measure. Only gamma rays will
pass through a heavy metal wall, glass windows will admit
all gammas and most betas, and plastic (Mylar) windows
are necessary to admit alpha particles. Counters of this
type, when properly calibrated, will measure the total
amount of radiation received by the body of the wearer.</p>
<h3>Proportional Counters</h3>
<p>This is a type of ionization chamber in which the intensity
of the electrical pulse it produces is proportional to the
energy of the incoming particle. This makes it possible to
record alpha particles and discriminate against gamma
rays.</p>
<div class="pb" id="Page_45">45</div>
<h3>Geiger-Müller Counters</h3>
<p>These have been widely used and are versatile in their
applications. The potential difference between the electrodes
in the Geiger-Müller tube (similar to an ionization chamber)
is high. A single alpha or beta particle ionizes some
of the gas within the chamber. In turn these ions strike
other gas molecules producing secondary ionization. The
result is an “avalanche” or high-intensity pulse of electricity
passing between the electrodes. These pulses can
be counted electrically and recorded on a meter at rates
up to several thousand per minute.</p>
<h3>Scintillation Counters</h3>
<p>Since the development of the photoelectric tube and the
photomultiplier tube (a combination of photoelectric cell
and amplifier), the scintillation counter has become the
most popular instrument for most purposes described in
this booklet. The flash of light produced when an individual
ionizing particle or ray strikes a sodium-iodide crystal is
noted by a photoelectric cell. The intensity of the flash is
a measure of the energy of the radiation, so the voltage of
the output of the photomultiplier tube is a measure of the
wavelength of the original gamma ray. The scintillation
counter can observe up to a million counts per minute and
discriminate sharply between gamma rays of different energies.
With proper windows it can be used for alpha or
beta counts as well.</p>
<h3>Solid State Counters</h3>
<p>The latest development is a tiny silicon (transistor-type)
diode detector that can be made as small as a grain of sand
and placed within the body with very little discomfort.</p>
<h3>Scanners</h3>
<p>Many of the applications described in this booklet require
accurate knowledge of the exact location of the radioactive
source within the body. Commonly a detecting tube
is used having a collimating shield so that it accepts only
that radiation that strikes it head-on. A motor-driven carrier
<span class="pb" id="Page_46">46</span>
moves the counter linearly at a slow rate. Radiation
is counted and whenever the count reaches the predetermined
amount—from one count to many—an electric
impulse causes a synchronously moving pen to make a dot
on a chart. The scanner, upon reaching the end of a line
moves down to the next line and starts over, eventually
producing a complete record of the radiation sources it
has passed over.</p>
<div class="pb" id="Page_47">47</div>
<h2 id="c33">SUGGESTED REFERENCES</h2>
<h3>Technical Books</h3>
<blockquote>
<p><i>Radioactive Isotopes in Medicine and Biology</i>, Solomon Silver, Lea
& Febiger, Philadelphia, Pennsylvania 19106, 1962, 347 pp.,
$8.00.</p>
<p><i>Atomic Medicine</i>, Charles F. Behrens and E. Richard King (Eds.),
The Williams & Wilkins Company, Baltimore, Maryland 21202,
1964, 766 pp., $18.00.</p>
<p><i>The Practice of Nuclear Medicine</i>, William H. Blahd, Franz K.
Bauer, and Benedict Cassen, Charles C. Thomas, Publisher,
Springfield, Illinois 62703, 1958, 432 pp., $12.50.</p>
<p><i>Progress in Atomic Medicine</i>, John H. Lawrence (Ed.), Grune &
Stratton, Inc., New York 10016, 1965, volume 1, 240 pp., $9.75.</p>
<p><i>Radiation Biology and Medicine</i>, Walter D. Claus (Ed.), Addison-Wesley
Publishing Company, Reading, Massachusetts 01867,
1958, 944 pp., $17.50. Part 7, Medical Uses of Atomic Radiation,
pp. 471-589.</p>
<p><i>Radioisotopes and Radiation</i>, John H. Lawrence, Bernard Manowitz,
and Benjamin S. Loeb, McGraw-Hill Book Company, New York
10036, 1964, 131 pp., $18.00. Chapter 1, Medical Diagnosis and
Research, pp. 5-45; Chapter 2, Medical Therapy, pp. 49-62.</p>
</blockquote>
<h3>Popular Books</h3>
<blockquote>
<p><i>Atoms Today and Tomorrow</i> (revised edition), Margaret O. Hyde,
McGraw-Hill Book Company, Inc., New York 10036, 1966,
160 pp., $3.25. Chapter 9, The Doctor and the Atom, pp. 79-101.</p>
<p><i>Atomic Energy in Medicine</i>, K. E. Halnan, Philosophical Library,
Inc., New York 10016, 1958, 157 pp., $6.00. (Out of print but
available through libraries.)</p>
<p><i>Teach Yourself Atomic Physics</i>, James M. Valentine, The Macmillan
Company, New York 10011, 1961, 192 pp., $1.95. (Out
of print but available through libraries.) Chapter X, Medical and
Biological Uses of Radioactive Isotopes, pp. 173-184.</p>
<p><i>Atoms for Peace</i>, David O. Woodbury, Dodd, Mead & Company,
New York 10016, 1965, 259 pp., $4.50. Pp. 174-191.</p>
<p><i>The Atom at Work</i>, Jacob Sacks, The Ronald Press Company, New
York 10010, 1956, 341 pp., $5.50. Chapter 13, Radioactive Isotopes
in Hospital and Clinic, pp. 244-264.</p>
</blockquote>
<h3>Articles</h3>
<blockquote>
<p>Ionizing Radiation and Medicine, S. Warren, <i>Scientific American</i>,
201: 164 (September 1959).</p>
<p>Nuclear Nurses Learn to Tame the Atom, W. McGaffin, <i>Today’s
Health</i>, 37: 62 (December 1959).</p>
<p>How Isotopes Aid Medicine in Tracking Down Your Ailments,
J. Foster, <i>Today’s Health</i>, 42: 40 (May 1964).</p>
<p>Nuclear Energy as a Medical Tool, G. W. Tressel, <i>Today’s Health</i>,
43: 50 (May 1965).</p>
</blockquote>
<div class="pb" id="Page_48">48</div>
<h3>Reports</h3>
<blockquote>
<p><i>Radioisotopes in Medicine</i> (SRIA-13), Stanford Research Institute,
Clearinghouse for Federal Scientific and Technical Information,
5285 Port Royal Road, Springfield, Virginia 22151, 1959, 180 pp.,
$3.00.</p>
</blockquote>
<p>The following reports are available from the Superintendent of
Documents, U. S. Government Printing Office, Washington, D. C.
20402.</p>
<blockquote>
<p><i>Isotopes and Radiation Technology</i> (Fall 1963), P. S. Baker, A. F.
Rupp, and Associates, Oak Ridge National Laboratory, U. S.
Atomic Energy Commission, 123 pp., $0.70.</p>
<p><i>Radioisotopes in Medicine</i> (ORO-125), Gould A. Andrews, Marshall
Brucer, and Elizabeth B. Anderson, 1956, 817 pp., $6.00.</p>
<p><i>Applications of Radioisotopes and Radiation in the Life Sciences</i>,
Hearings before the Subcommittee on Research, Development,
and Radiation of the Joint Committee on Atomic Energy, 87th
Congress, 1st Session, 1961, 513 pp., $1.50; Summary Analysis
of the Hearings, 23 pp., $0.15.</p>
</blockquote>
<h3>Motion Pictures</h3>
<p>Available for loan without charge from the AEC Headquarters
Film Library, Division of Public Information, U. S. Atomic Energy
Commission, Washington, D. C. 20545 and from other AEC film
libraries.</p>
<blockquote>
<p><i>Radioisotope Applications in Medicine</i>, 26 minutes, black and white,
sound, 1964. Produced by the Educational Broadcasting Corporation
under the joint direction of the U. S. Atomic Energy Commission’s
Divisions of Isotopes Development and Nuclear Education
and Training, and the Oak Ridge Institute of Nuclear Studies.
This film traces the development of the use of radioisotopes
and radiation in the field of medicine from the early work of
Hevesy to the present. Descriptions of the following are given:
study of cholesterol and arteriosclerosis; cobalt labeled vitamin
B₁₂ used to study pernicious anemia; history of iodine radioisotopes
and the thyroid; brain tumor localization; determination
of body fluid volumes; red cell lifetime; and use of radioisotopes
for the treatment of various diseases.</p>
<p><i>Medicine</i>, 20 minutes, sound, color, 1957. Produced by the U. S.
Information Agency. Four illustrations of the use of radioactive
materials in diagnosis and therapy are given: exact preoperative
location of brain tumor; scanning and charting of thyroids;
cancer therapy research; and the study of blood diseases and
hardening of the arteries.</p>
<p><i>Radiation Protection in Nuclear Medicine</i>, 45 minutes, sound,
color, 1962. Produced by the Fordel Films for the Bureau of
Medicine and Surgery of the U. S. Navy. This semitechnical film
demonstrates the procedures devised for naval hospitals to
protect against the gamma radiation emitted from materials
used in radiation therapy.</p>
</blockquote>
<div class="pb" id="Page_49">49</div>
<p>The following films in the Magic of the Atom Series were produced
by the Handel Film Corporation. They are each 12½ minutes long,
have sound, and are in black and white.</p>
<blockquote>
<p><i>The Atom and the Doctor</i> (1954) shows three applications of radioisotopes
in medicine: testing for leukemia and other blood disorders
with radioiron; diagnosis of thyroid conditions with
radioiodine; and cancer research and therapy with radiogallium.</p>
<p><i>The Atom in the Hospital</i> (1961) (available in color and black and
white) illustrates the following facilities at the City of Hope
Medical Center in Los Angeles: the stationary cobalt source
that is used to treat various forms of malignancies; a rotational
therapy unit called the “cesium ring”, which revolves around
the patient and focuses its beam on the diseased area; and the
total-body irradiation chamber for studying the effects of radiation
on living things. Research with these facilities is explained.</p>
<p><i>Atomic Biology for Medicine</i> (1956) explains experiments performed
to discover effects of radiation on mammals.</p>
<p><i>Atoms for Health</i> (1956) outlines two methods of diagnosis and
treatment possible with radiation: a diagnostic test of the liver,
and cancer therapy with a radioactive cobalt device. Case
histories are presented step-by-step.</p>
<p><i>Radiation: Silent Servant of Mankind</i> (1956) depicts four uses of
controlled radiation that can benefit mankind: bombardment of
plants from a radioactive cobalt source to induce genetic changes
for study and crop improvement; irradiation of deep-seated
tumors with a beam from a particle accelerator; therapy of
thyroid cancer with radioactive iodine; and possibilities for
treating brain tumors.</p>
</blockquote>
<div class="pb" id="Page_50">50</div>
<h2 id="c34">PHOTO CREDITS</h2>
<p>Cover Courtesy Brookhaven National Laboratory</p>
<table class="center">
<tr><td class="l">Page</td></tr>
<tr><td class="l">1 </td><td class="l">General Electric Company</td></tr>
<tr><td class="l">2, 3, & 4 </td><td class="l"><i>Discovery of the Elements.</i> Mary Elvira Weeks, Journal of Chemical Education</td></tr>
<tr><td class="l">6 </td><td class="l">Nobel Institute</td></tr>
<tr><td class="l">12 </td><td class="l">Chicago Wesley Memorial Hospital (main photo)</td></tr>
<tr><td class="l">13 </td><td class="l">Lawrence Radiation Laboratory (LRL)</td></tr>
<tr><td class="l">14 </td><td class="l">Brookhaven National Laboratory</td></tr>
<tr><td class="l">17 </td><td class="l">LRL</td></tr>
<tr><td class="l">21 </td><td class="l">LRL</td></tr>
<tr><td class="l">22 </td><td class="l">Los Alamos Scientific Laboratory</td></tr>
<tr><td class="l">24 </td><td class="l">LRL</td></tr>
<tr><td class="l">28 </td><td class="l">Argonne National Laboratory</td></tr>
<tr><td class="l">39 </td><td class="l">Paul V. Harper, M. D.</td></tr>
<tr><td class="l">41 </td><td class="l">University of Texas, M. D. Anderson Hospital and Tumor Institute</td></tr>
</table>
<div class="pb" id="Page_51">51</div>
<p>This booklet is one of the “Understanding the Atom”
Series. Comments are invited on this booklet and others
in the series; please send them to the Division of Technical
Information, U. S. Atomic Energy Commission, Washington,
D. C. 20545.</p>
<p>Published as part of the AEC’s educational assistance
program, the series includes these titles:</p>
<dl class="undent"><br/><i>Accelerators</i>
<br/><i>Animals in Atomic Research</i>
<br/><i>Atomic Fuel</i>
<br/><i>Atomic Power Safety</i>
<br/><i>Atoms at the Science Fair</i>
<br/><i>Atoms in Agriculture</i>
<br/><i>Atoms, Nature, and Man</i>
<br/><i>Books on Atomic Energy for Adults and Children</i>
<br/><i>Careers in Atomic Energy</i>
<br/><i>Computers</i>
<br/><i>Controlled Nuclear Fusion</i>
<br/><i>Cryogenics, The Uncommon Cold</i>
<br/><i>Direct Conversion of Energy</i>
<br/><i>Fallout From Nuclear Tests</i>
<br/><i>Food Preservation by Irradiation</i>
<br/><i>Genetic Effects of Radiation</i>
<br/><i>Index to the UAS Series</i>
<br/><i>Lasers</i>
<br/><i>Microstructure of Matter</i>
<br/><i>Neutron Activation Analysis</i>
<br/><i>Nondestructive Testing</i>
<br/><i>Nuclear Clocks</i>
<br/><i>Nuclear Energy for Desalting</i>
<br/><i>Nuclear Power and Merchant Shipping</i>
<br/><i>Nuclear Power Plants</i>
<br/><i>Nuclear Propulsion for Space</i>
<br/><i>Nuclear Reactors</i>
<br/><i>Nuclear Terms, A Brief Glossary</i>
<br/><i>Our Atomic World</i>
<br/><i>Plowshare</i>
<br/><i>Plutonium</i>
<br/><i>Power from Radioisotopes</i>
<br/><i>Power Reactors in Small Packages</i>
<br/><i>Radioactive Wastes</i>
<br/><i>Radioisotopes and Life Processes</i>
<br/><i>Radioisotopes in Industry</i>
<br/><i>Radioisotopes in Medicine</i>
<br/><i>SNAP, Nuclear Space Reactors</i>
<br/><i>Sources of Nuclear Fuel</i>
<br/><i>Space Radiation</i>
<br/><i>Spectroscopy</i>
<br/><i>Synthetic Transuranium Elements</i>
<br/><i>The Atom and the Ocean</i>
<br/><i>The Chemistry of the Noble Gases</i>
<br/><i>The Elusive Neutrino</i>
<br/><i>The First Reactor</i>
<br/><i>The Natural Radiation Environment</i>
<br/><i>Whole Body Counters</i>
<br/><i>Your Body and Radiation</i>
<p>A single copy of any one booklet, or of no more than three
different booklets, may be obtained free by writing to:</p>
<p class="center"><b class="ss">USAEC, P. O. BOX 62, OAK RIDGE, TENNESSEE<span class="hst"> 37830</span></b></p>
<p>Complete sets of the series are available to school and
public librarians, and to teachers who can make them
available for reference or for use by groups. Requests
should be made on school or library letterheads and indicate
the proposed use.</p>
<p>Students and teachers who need other material on specific
aspects of nuclear science, or references to other
reading material, may also write to the Oak Ridge address.
Requests should state the topic of interest exactly, and the
use intended.</p>
<p>In all requests, include “Zip Code” in return address.</p>
<p class="tbcenter"><span class="small">Printed in the United States of America
<br/>USAEC Division of Technical Information Extension, Oak Ridge, Tennessee</span></p>
<h2 id="c35">FOOTNOTES</h2>
<div class="fnblock"><div class="fndef"><SPAN class="fn" id="fn_1" href="#fr_1">[1]</SPAN>The early dangers from use of X rays, due to incomplete
understanding and inadequate shielding, have now been eliminated.</div>
<div class="fndef"><SPAN class="fn" id="fn_2" href="#fr_2">[2]</SPAN>Gamma rays are high-energy electromagnetic radiation.</div>
<div class="fndef"><SPAN class="fn" id="fn_3" href="#fr_3">[3]</SPAN>Alpha particles are large positively charged particles, identical
to helium nuclei. For definitions of unfamiliar words see <i>Nuclear
Terms, A Brief Glossary</i>, a companion booklet in this series.</div>
<div class="fndef"><SPAN class="fn" id="fn_4" href="#fr_4">[4]</SPAN>For detailed descriptions of these waves and particles, see
<i>Our Atomic World</i>, a companion booklet in this series.</div>
<div class="fndef"><SPAN class="fn" id="fn_5" href="#fr_5">[5]</SPAN>An equivalent statement is that nuclei of isotopes have the
same number of protons but different numbers of neutrons.</div>
<div class="fndef"><SPAN class="fn" id="fn_6" href="#fr_6">[6]</SPAN>See <SPAN href="#c32">Appendix</SPAN> for a description of types of radiation-detection instruments.</div>
<div class="fndef"><SPAN class="fn" id="fn_7" href="#fr_7">[7]</SPAN>See <i>Radioisotopes and Life Processes</i>, another booklet in this series, for a discussion of one area of biomedical research.</div>
<div class="fndef"><SPAN class="fn" id="fn_8" href="#fr_8">[8]</SPAN>A positron is an “antielectron”. It has the mass of an electron
but a positive charge.</div>
<div class="fndef"><SPAN class="fn" id="fn_9" href="#fr_9">[9]</SPAN>A collimator is a focusing device consisting of a series of slits
between blocks of shielding material. Consult the <SPAN href="#c32">Appendix</SPAN> for
descriptions of other instruments mentioned here.</div>
<div class="fndef"><SPAN class="fn" id="fn_10" href="#fr_10">[10]</SPAN>The superscript m after this isotope indicates an excited state
of the atom.</div>
<div class="fndef"><SPAN class="fn" id="fn_11" href="#fr_11">[11]</SPAN>As radioactive nuclei disintegrate, they change to other radioactive
forms—their “daughter” products. Every radioisotope is
thus part of a chain or series of steps that ends with a stable form.
Technetium-99<sup>m</sup> is a daughter product of molybdenum-99; it decays
by a process known as isomeric transition to a state of
lower energy and longer half-life.</div>
<div class="fndef"><SPAN class="fn" id="fn_12" href="#fr_12">[12]</SPAN>The curie is the basic unit of radiation intensity. One curie is
approximately the amount of radioactivity in 1 gram of radium.</div>
<div class="fndef"><SPAN class="fn" id="fn_13" href="#fr_13">[13]</SPAN>See Your Body and Radiation and The Genetic Effects of Radiation,
other booklets in this series, for detailed explanations of
radiation effects.</div>
<div class="fndef"><SPAN class="fn" id="fn_14" href="#fr_14">[14]</SPAN>The use of radium is not under AEC control.</div>
<div class="fndef"><SPAN class="fn" id="fn_15" href="#fr_15">[15]</SPAN>One family of measuring instruments is described in
<br/><i>Whole Body Counters</i>,
<br/>another booklet in this series. These are large devices that make use of scintillating crystals or liquids.</div>
</div>
<h2 id="c36">Transcriber’s Notes</h2>
<ul><li>Retained publication information from the printed edition: this eBook is public-domain in the country of publication.</li>
<li>Where possible, UTF superscript and subscript numbers are used; some e-reader fonts may not support these characters.</li>
<li>In the text version only, underlined or italicized text is delimited by _underscores_.</li>
<li>In the text version only, superscript text is preceded by caret and delimited by ^{brackets}.</li>
<li>In the text version only, subscripted text is preceded by underscore and delimited by _{brackets}.</li></ul>
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