Essentials of Nuclear Medicine Imaging: Expert Consult - Online and Print, 6e

603 Pages·2012·52.96 MB·English

by  Fred A. Mettler Jr. MD MPH, Milton J. Guiberteau MD

Essentials of
Nuclear
Medicine
Imaging
th
6
Edition
FRED A. METTLER, JR., MD, MPH
Imaging Service
New Mexico Veteran’s Affairs Heath Care System
Clinical and Emeritus Professor
University of New Mexico School of Medicine
Albuquerque, New Mexico
MILTON J. GUIBERTEAU, MD
Professor of Clinical Radiology and Nuclear Medicine
University of Texas Medical School at Houston
Academic Chief, Department of Medical Imaging
Director of Nuclear Medicine
St. Joseph Medical Center
Houston, Texas
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
th
ESSENTIALS OF NUCLEAR MEDICINE IMAGING, 6 Edition ISBN: 978-1-4557-0104-9
Copyright © 2012, 2006, 1998, 1991, 1985, 1983 by Saunders, an imprint of Elsevier Inc.
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Notice
Knowledge and best practice in this feld are constantly changing. As new research and experience
broaden our knowledge, changes in practice, treatment, and drug therapy may become necessary or
appropriate. Readers are advised to check the most current information provided (i) on p rocedures
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dose or formula, the method and duration of administration, and contraindications. It is the
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Library of Congress Cataloging-in-Publication Data
Mettler, Fred A., 1945-
Essentials of nuclear medicine imaging / Fred A. Mettler Jr., Milton
J. Guiberteau. -- 6th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4557-0104-9 (pbk. : alk. paper)
I. Guiberteau, Milton J. II. Title.
[DNLM: 1. Nuclear Medicine--methods. 2. Radionuclide Imaging. 3.
Radiopharmaceuticals. 4. Radiotherapy. WN 445]
616.07575--dc23
2011040394
Acquisitions Editor: Don Scholz
Developmental Editor: Lora Sickora
Publishing Services Manager: Anne Altepeter
Project Managers: Kiruthiga Kasthuri/Louise King
Marketing Manager: Tracie Pasker
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
To our parents, our families,
and those who spend their time teaching residents
Acknowledgments
We would like to recognize the many residents, provided images, background material, and sug-
technologists, and others who provided sugges- gestions. We also would like to thank R uthAnne
tions, as well as a number of our colleagues who Bump for her help with the illustrations.
ix
Preface
Six years have elapsed since publication of the radiopharmaceuticals. We have also limited
ffth edition of Nuclear Medicine Imaging, and content on less common and outmoded proce-
it has been 34 years since the frst edition. In dures, and removed outdated content. We have
this sixth edition, we have made revisions that added new material on procedure guidelines
refect changes in the current practice of nuclear (such as GI emptying studies and Na-18F bone
medicine and molecular imaging, while main- scanning). The expanded use of PET has per-
taining our focus on the essential elements. We mitted material on PET and PET/CT imaging
have also endeavored to retain the book’s prior for CNS and cardiac applications to be relo-
extent and affordability. Since the previous edi- cated to those organ-specifc chapters, and we
tion, there has been continued change, not only have organized separate chapters on non-PET
in the patterns of use of existing nuclear medi- and PET neoplasm imaging. Information rela-
cine studies but also notably in the evolution tive to the duties and expectations of an autho-
of radiopharmaceuticals and instrumentation, rized user (AU) has been updated and clarifed.
such as the widespread use of hybrid imaging We have noted that residents supplement
(especially PET/CT and SPECT/CT). their clinical case experience with atlases and
The progressive integration of traditional casebooks. There are more than 400 fgures
nuclear medicine techniques with those of in this edition, and about 40% of the illustra-
diagnostic radiology, providing both anatomic tions are entirely new. We have also included
and functional information on a single set of in the text, where appropriate, information on
coregistered images, has added powerful tools how to use radiation ( dosing) wisely. At the
to the diagnosis of disease and the assessment end of the text, we have updated and revised
of treatment effectiveness. At the same time, it the Unknown Case Sets in a more familiar and,
has increased the need for imagers to broaden hopefully, instructive format. Review of the
their imaging skills. These considerations are sets will allow readers to assess their knowledge
addressed in this edition. Further, enhanced in a commonly employed format and to gain
equipment automation has allowed informa- familiarity with commonly encountered nuclear
tion about quality control to be condensed and imaging entities.
included in Chapters 1 and 2.
We have updated all chapters to include Fred A. Mettler, Jr.
recent developments in instrumentation and Milton J. Guiberteau
vii
Radioactivity,
Radionuclides, and
1
Radiopharmaceuticals
BASIC ISOTOPE NOTATION Fluorine-18 and Other Positron Emitters
Nuclear Stability and Decay Monoclonal Antibodies
RADIONUCLIDE PRODUCTION Investigational Radiopharmaceuticals
RADIOACTIVE DECAY RADIOPHARMACY QUALITY CONTROL
RADIONUCLIDE GENERATOR SYSTEMS Generator and Radionuclide Purity
RADIONUCLIDES AND Radiochemical Labeling
RADIOPHARMACEUTICALS FOR IMAGING UNSEALED RADIONUCLIDES USED FOR
Technetium-99m THERAPY
Iodine-123 and -131 Phosphorus-32, Yttrium-90, and Gold-198
Xenon-133 Iodine-131
Gallium-67 Strontium-89, Samarium-153, and
Indium-111 Rhenium-186
Thallium-201
BASIC ISOTOPE NOTATION with odd numbers of neutrons and protons are
The atom may be thought of as a collection of usually unstable. Nuclear instability may result
protons, neutrons, and electrons. The protons from either neutron or proton excess. Nuclear
and neutrons are found in the nucleus, and decay may involve a simple release of energy
shells of electrons orbit the nucleus with discrete from the nucleus or may actually cause a change
energy levels. The number of neutrons is usually in the number of protons or neutrons within
designated by N. The number of protons is rep- the nucleus. When decay involves a change in
resented by Z (also called the atomic number). the number of protons, there is a change of ele-
The atomic mass number, or the total number ment. This is termed a transmutation. Isotopes
of nuclear particles, is represented by A and is attempting to reach stability by emitting radia-
simply the sum of N and Z. The symbolism used tion are radionuclides.
to designate atoms of a certain element having Several mechanisms of decay achieve stabil-
the chemical symbol X is given by ZAXN. For ity. One of these is alpha-particle emission. In
example, the notation 15331I78 refers to a certain this case, an alpha (α) particle, consisting of two
isotope of iodine. In this instance, 131 refers protons and two neutrons, is released from the
to the total number of protons and neutrons nucleus, with a resulting decrease in the atomic
in the nucleus. By defnition, all isotopes of a mass number (A) by four and reduction of both
given element have the same number of protons Z and N by two. The mass of the released alpha
and differ only in the number of neutrons. For particles is so great that they travel only a few
example, all isotopes of iodine have 53 protons. centimeters in air and are unable to penetrate
even thin paper. These properties cause alpha-
Nuclear Stability and Decay particle emitters to be essentially useless for
A given element may have many isotopes, and imaging purposes.
some of these isotopes have unstable nuclear Beta-particle emission is another process for
confgurations of protons and neutrons. These achieving stability and is found primarily in
isotopes often seek greater stability by decay or nuclides with a neutron excess. In this case, a
disintegration of the nucleus to a more stable beta (β−) particle (electron) is emitted from the
form. Of the known stable nuclides, most have nucleus accompanied by an antineutrino; as a
even numbers of neutrons and protons. Nuclides result, one of the neutrons may be thought of as
1
2   Chapter 1  n Radioactivity, Radionuclides, and Radiopharmaceuticals
A A
X X
Z Z
A A
Y Y
Z+1 Z-1
Beta particle emission Electron capture
(Z increases by 1, N decreases by 1) (Z decreases by 1, N increases by 1)
A A
X X
Z Z
A A
Y X
Z-1 Z
Positron emission Isomeric transition
(Z decreases by 1, N increases by 1) (no change in N or Z)
Figure 1-1. Decay schemes of
radionuclides from unstable states
(top line of each diagram) to more
stable states (bottom line).
being transformed into a proton, which remains unchanged (see Fig. 1-1). Electron capture may
in the nucleus. Thus, beta-particle emission be accompanied by gamma emission and is
decreases the number of neutrons (N) by one always accompanied by characteristic radiation,
and increases the number of protons (Z) by one, either of which may be used in imaging.
so that A remains unchanged (Fig. 1-1). When If, in any of these attempts at stabilization, the
Z is increased, the arrow in the decay scheme nucleus still has excess energy, it may be emit-
shown in Figure 1-1 points toward the right, and ted as nonparticulate radiation, with Z and N
the downward direction indicates a more stable remaining the same. Any process in which energy
state. The energy spectrum of beta-particle emis- is given off as gamma rays and in which the num-
sion ranges from a certain maximum down to bers of protons and neutrons are not changed
zero; the mean energy of the spectrum is about is called isomeric transition (see Fig. 1-1). An
one third of the maximum. A 2-MeV beta par- alternative to isomeric transition is internal con-
ticle has a range of about 1 cm in soft tissue and version. In internal conversion, the excess energy
is therefore not useful for imaging purposes. of the nucleus is transmitted to one of the orbital
Electron capture occurs in a neutron-defcient electrons; this electron may be ejected from the
nuclide when one of the inner orbital electrons is atom, which is followed by characteristic radia-
captured by a proton in the nucleus, forming a tion when the electron is replaced. This process
neutron and a neutrino. This can occur when not usually competes with gamma-ray emission and
enough energy is available for positron emission, can occur only if the amount of energy given to
and electron capture is therefore an alternative the orbital electron exceeds the binding energy
to positron decay. Because a nuclear proton is of that electron in its orbit.
essentially changed to a neutron, N increases by The ratio of internal conversion electrons to
one, and Z decreases by one; therefore, A remains gamma-ray emissions for a particular radioisotope
Chapter 1  n Radioactivity, Radionuclides, and Radiopharmaceuticals   3
99m
Tc (6.03 h)
142.7 keV
Gamma 1
140.5 keV
Gamma 2 Gamma 3
99 9
Tc (2.1 x 10 yr)
0 keV
98.6% 1.4%
Figure 1-2. Decay  scheme  of 
technetium-99m.
is designated by the symbol α. (This should decay scheme again indicates a more stable
not be confused with the symbol for an alpha state, and its leftward direction indicates that
particle.) For an isotope such as technetium- Z is decreased. Positron emission cannot occur
99m
99m ( Tc), α is low, indicating that most unless at least 1.02 MeV of energy is available
emissions occur as gamma rays with little to the nucleus.
internal conversion. A low conversion ratio When a positron is emitted, it travels for a
is preferable for in-vivo usage because it implies short distance from its site of origin, gradually
a greater number of gamma emissions for imag- losing energy to the tissue through which it
ing and a reduced number of conversion elec- moves. When most of its kinetic energy has been
trons, which are absorbed by the body and thus lost, the positron reacts with a resident electron
add to the patient’s radiation dose. in an annihilation reaction. This reaction gener-
In many instances, a gamma-ray photon is ates two 511-keV gamma photons, which are
emitted almost instantaneously after particulate emitted in opposite directions at about (but not
decay. If there is a measurable delay in the emis- exactly) 180 degrees from each other (Fig. 1-3).
sion of the gamma-ray photon and the resulting
decay process is an isomeric transition, this inter- RADIONUCLIDE PRODUCTION
mediate excited state of the isotope is referred to Most radioactive material that does not occur
as metastable. The most well-known metastable naturally can be produced by particulate bom-
99m
isotope is Tc (the m refers to metastable). This bardment or fssion. Both methods alter the
isotope decays by isomeric transition to a more neutron-to-proton ratio in the nucleus to pro-
stable state, as indicated in Figure 1-2. In the duce an unstable isotope. Bombardment essen-
decay scheme, the arrows point straight down, tially consists of the irradiation of the nuclei
99m
showing that there is no change in Z. Also, Tc of selected target elements with neutrons in a
may decay by one of several routes of gamma- nuclear reactor or with charged particles (alpha
ray emission. particles, protons, or deuterons) from a cyclo-
In cases in which there are too many protons tron. Bombardment reactions may be summa-
in the nucleus (a neutron-defcient nuclide), rized by equations in which the target element
decay may proceed in such a manner that a pro- and bombarding particle are listed on the left
ton may be thought of as being converted into side of the equation and the product and any
+
a neutron. This results in positron (β ) emis- accompanying particulate or gamma emissions
sion, which is always accompanied by a neu- are indicated on the right. For example,
trino. This obviously increases N by one and
A A+1
decreases Z by one, again leaving A unchanged ZX+n (neutron)→Z X+γ or more specifically
98 99
(see Fig. 1-1). The downward arrow in the 42Mo+n (neutron)→ 42Mo+ γ
4   Chapter 1  n Radioactivity, Radionuclides, and Radiopharmaceuticals
are identical, and thus radionuclides are not as
easily separated.
Fission isotopes are simply the daughter prod-
511 keV photons 235
ucts of nuclear fssion of uranium-235 ( U) or
239
plutonium-239 ( Pu) in a reactor and represent
a multitude of radioactive materials, with atomic
numbers in the range of roughly half that of
235 131
U. These include iodine-131 ( I), xenon-133
133 90
( Xe), strontium-90 ( Sr), m olybdenum-99
⫺
β 99 137
( Mo), and cesium-137 ( Cs), among o thers.
Because many of these isotopes are present
180⬚ ⫹/⫺ 0.25⬚
⫹
β
together in the fssion products, the desired iso-
tope must be carefully isolated to exclude as
many contaminants as possible. Although this
is sometimes diffcult, many carrier-free isotopes
are produced in this manner.
Neutron bombardment and nuclear fssion
almost always produce isotopes with neutron
excess, which decay by beta emission. Some
99
isotopes, such as Mo, may be produced by
either method. Cyclotron-produced isotopes are
+
Figure 1-3. Positron decay. After the positron (β ) is emit-
usually neutron defcient and decay by electron
ted from the radionuclide, it travels some distance before
− capture or positron emission. Some common
interacting with an electron (β ) and undergoing annihi-
lation, resulting in emission of two 511-keV photons at examples of cyclotron-produced isotopes include
180-degrees from each other. 123 18
iodine-123 ( I), fuorine-18 ( F), gallium-67
67 111
( Ga), indium-111 ( In), and thallium-201
201
( Tl). In general, cyclotron-generated radio-
These equations may be further abbreviated nuclides are more expensive than are those pro-
using parenthetical notation. The molybde- duced by neutron bombardment or fssion.
num reaction presented previously is thus rep- Positron-emitting radionuclides are most com-
98 99
resented as Mo (n, γ) Mo. The target and monly produced in cyclotrons by bombarding
product are noted on the outside of the paren- a stable element with protons, deuterons, or
theses, which contain the bombarding particle helium nuclei. The produced radionuclides have
on the left and any subsequent emissions on the an excess of protons and decay by the emission
right. of positrons.
Once bombardment is completed, the daugh-
ter isotope must be physically separated from RADIOACTIVE DECAY
any remaining and unchanged target nuclei, as The amount of radioactivity present (the num-
well as from any target contaminants. Thus, it is ber of disintegrations per second) is referred
obvious that the completeness of this fnal sepa- to as activity. In the past, the unit of radioac-
ration process and the initial elemental purity of tivity has been the curie (Ci), which is 3.7 ×
10
the target are vital factors in obtaining a prod- 10 disintegrations per second. Because
uct of high specifc activity. Because cyclotron the curie is an inconvenient unit, it has been
isotope production almost always involves a largely replaced by an international unit called
transmutation (change of Z) from one element a becquerel (Bq), which is one disintegration
to another, this process aids greatly in the sepa- per second. Conversion tables are found in
ration of the radionuclides to obtain carrier-free A ppendixes B-1 and B-2. Specifc activity
isotopes (i.e., isotopes that have none of the refers to the activity per unit mass of material
stable element accompanying them). Radionu- (mCi/g or Bq/g). For a carrier-free isotope, the
clides made by neutron bombardment, which longer the half-life of the isotope, the lower is
does not result in a change of elemental spe- its specifc activity.
98 99
cies (e.g., Mo [n, γ] Mo), are not carrier free Radionuclides decay in an exponential fash-
because the chemical properties of the products ion, and the term half-life is often used casually
Chapter 1  n Radioactivity, Radionuclides, and Radiopharmaceuticals   5
to characterize decay. Half-life usually refers to humans, one needs to know the physical half-
the physical half-life, which is the amount of life of the radioisotope used as a tag or label
time necessary for a radionuclide to be reduced as well as the biologic half-life of the tagged
to half of its existing activity. The physical half- compound. If these are known, the following
life (Tp) is equal to 0.693/λ, where λ is the decay formula can be used to calculate the effective
constant. Thus, λ and the physical half-life half-life:
have characteristic values for each radioactive
Te = (Tp ×Tb) / (Tp +Tb)
nuclide. Decay tables for various radionuclides
are presented in Appendix C. where
A formula that the nuclear medicine physi-
Te = effective half-life
cian should be familiar with is the following:
Tp =physical half-life
A=A0e ‐ 0.693 / Tp (t) Tb = biologic half-life
This formula can be used to fnd the activity If the biologic half-life is 3 hours and the
(A) of a particular radioisotope present at a physical half-life is 6 hours, then the effective
given time (t) and having started with activity half-life is 2 hours. Note that the effective half-
(A0) at time 0. For instance, if you had 5 mCi life is always shorter than either the physical or
99m
(185 MBq) of Tc at 9 am today, how much biologic half-life.
would remain at 9 am tomorrow? In this case,
99m
T
p of Tc is 6 hours, t is 24 hours, and e is a RADIONUCLIDE GENERATOR
mathematical constant. Thus, SYSTEMS
A number of radionuclides of interest in nuclear
− 0.693
(t) medicine are short-lived isotopes that emit only
Tp
A=A0e
gamma rays and decay by isomeric transition.
− 0.693 Because it is often impractical for an imaging
(24 hours)
A=A0e6 hours
laboratory to be located near a reactor or a
− 0.693 cyclotron, generator systems that permit on-site
(24 hours)
A=5 mCi e6 hours
availability of these isotopes have achieved wide
use. Some isotopes available from generators
− 0.1155 (24 hours)
A=5 mCi e 113m
include technetium-99m, indium-113m ( In),
81m 82
− 2.772 krypton-81m ( Kr), rubidium-82 ( Rb),
A=5 mCi e
87m 68
strontium-87m ( Sr), and gallium-68 ( Ga).
1 99
Inside the most common generator ( Mo-
A=5 mCi e2.772
99m
Tc), a radionuclide “parent” with a relatively
( )
1
long half-life is frmly affxed to an ion exchange
A=5 mCi e 15.99
99 99m
column. A Mo- Tc generator consists of an
99
A=0.31 mCi alumina column on which Mo is bound. The
parent isotope (67-hour half-life) decays to its
99m 99m
Thus, after 24 hours, the amount of Tc radioactive daughter, Tc, which is a differ-
remaining is 0.31 mCi (11 MBq). ent element with a shorter half-life (6 hours).
In addition to the physical half-life or physical Because the daughter is only loosely bound on
decay of a radionuclide, two other half-life terms the column, it may be removed, or washed off,
are commonly used. Biologic half-life refers to with an elution liquid such as normal (0.9%)
99 99m
the time it takes an organism to eliminate half saline. Wet and dry Mo- Tc generator sys-
of an administered compound or chemical on a tems are available and differ only slightly. A wet
strictly biologic basis. Thus, if a stable chemi- system has a saline reservoir and a vacuum vial
cal compound were given to a person, and half that draws saline across the column. With a dry
of it were eliminated by the body (perhaps in system, a specifc amount of saline in a vial is
the urine) within 3 hours, the biologic half-life placed on the generator entry port and drawn
would be 3 hours. The effective half-life incor- across by a vacuum vial (Fig. 1-4).
porates both the physical and biologic half- After the daughter is separated from the col-
lives. Therefore, when speaking of the effective umn, the buildup process is begun again by the
half-life of a particular radiopharmaceutical in residual parent isotope. Uncommonly, some of