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CHAPTER 16 Radioisotopes and Radiation Protection
327
To determine the equivalent dose rate (specified in
µSv/hr at a particular distance from a person injected
with a specific amount of 18F), the shielding planner
must make use of a “measured” quantity called the dose
rate constant. Its value is 6.96 µSv/hr at a distance of 1 m
per mCi of 18F. Thus, if the patient did not self-attenuate
any of the 18F radiation, then just after a 15-mCi injection, the equivalent dose rate 1 m away would be approximately 7 3 15 5 105 µSv/hr. At greater distances,
the inverse square law can be applied to obtain a value.
For example, at a separation of 4 meters (approximately
13 feet), the initial high-energy photons’ equivalent
dose rate in the absence of any shielding or attenuation
reduces to:
2
105/4 6.6 Sv/hr
(0.66 mrem/hr)
Distance is thus seen to be a very powerful tool of
radiation protection. A well-designed facility takes especial advantage of this. Returning to the injected patient,
there are other facilitators of radiation protection at
hand. Both the patient and nature are responsible for
this. It has been found from multiple measurements
that the body can absorb a substantial amount of 18F
annihilation radiation.
Thus the mean maximum equivalent dose rate at 1 m
from the patient per mCi (37 MBq) injected just after
the injection is not 6.96 µSv/hr, as it would be for an
unshielded point source of radiation; rather, it has been
determined to be approximately 3 µSv/hr per mCi due
to average patient self-attenuation.1 At a distance of 4 m
from the patient just after a 15 mCi injection, the
equivalent dose rate is now given from the inverse
square law by:
(15 3)/4 2.8 Sv/hr
2
Nature’s contribution to the radiation protection
effort is that 18F has a short half-life. Therefore, the
15 mCi dose injected at 2:00 p.m. will, because of natural radiation decay, be approximately 69%* as strong
60 minutes later for a 3:00 p.m. scan starting time. In
actuality, the equivalent dose delivered by the “hot” patient while waiting during the prep time at a distance
of 4 m is less than 2.8 µSv because of the continuing
*Radioactive decay factor after a full 60 minutes is obtained from
–(0.693 3 60/110)
(e
) 5 0.69.
decrease of the Fluorine-18 activity. If not 2.8 µSv, then
what dose equivalent would a person at this 4 m distance on average receive in 60 minutes? It must be some
percentage that lies between 100% and 69% of 2.8.
Using the mathematics of radioactive decay** yields an
average value of approximately 83%, or a correction
factor of 0.83. Consequently, the equivalent dose at a
distance of 4 m that could be received by a technologist
who is continuously present at this 4 m location (i.e.,
occupancy level T 5 1) from a 1-hour prep patient in
the absence of any added shielding is:
0.83 2.8 2.3 Sv
Over the course of a week, assuming a total of
35 patients, then, with all other conditions remaining
the same, this technologist will accumulate from prep
patients an equivalent dose of:
35 2.3 81 Sv (8.1 millirem)
Over 50 weeks, this would add up to about 4000 µSv
(400 mrem) from prep patients alone. However, prep patients are not the only sources of high-energy radiation
dose to PET-CT personnel. There is also the scan patient
and, to a much lesser extent, the patient’s toilet and the hot
lab. The contributions of all sources of radiation dose need
to be factored into the facility’s design and shielding plan.
Consider the scan patient in some detail. As always,
it is desirable to have a good distance, if at all possible,
between personnel and the radiation source. That is
usually not feasible especially if the PET-CT suite is being fit into a preexisting area. So, considering the
scanned patient first, let it be assumed that there is a
separation of only 3.3 m from the scan patient’s midline
to the location of the PET-CT technologist. In the absence of additional shielding, what could be the equivalent dose rate from this patient? The first factor to be
aware of is the lesser activity remaining in the patient
due to physical decay, namely about 69% of the original
15 mCi. However, this is not the whole story. The prep
patient is encouraged to void just before being scanned.
What this means is that the residual 18F in the patient’s
body at the start of the scan is less than 69% of the
original activity. If it is assumed that approximately
**Average Decay correction factor over a period of 60 minutes 5
[1.443 3 (110/60) 3 (12 0.69)] ≈ 0.83 where 1.443 3 110
minutes is the average lifetime of the Fluorine-18 nucleus in a
radioactive sample.
328
CHAPTER 16 Radioisotopes and Radiation Protection
20% more was removed by voiding, then at the start of
the scan, the activity within the patient is roughly just
50% of the original activity, namely: 0.5 3 15 5 7.5 mCi.
If there were no other considerations,* then at the start
of the scan the equivalent dose rate at the location of the
technologist with no shielding would be:
µµSv
hr
2
µµ(7.5 mCi 3 per mCi)/(3.3) 2 Sv/hr
(0.2 mrem/hr)
However, the radioactivity within the patient continues to decay all throughout the approximate 1 hour
between voiding and their departure. Therefore, the
mean equivalent dose to the technologist from the
scanned patient during this additional hour of isotope
decay, as determined before, will actually be 0.83 3
2 µSv/hr, 5 1.7 µSv. Over the course of a week, this
approximately amounts to: 35 patients 3 1.7 5 60 µSv.
At 50 weeks, this totals 3000 µSv (300 mrem). Then, the
*In this discussion, any degree of shielding provided by the
scanner itself is being neglected.
PET/CT
control
room
3.3 meters
View
window
unshielded technologist could receive an annual equivalent dose of 4000 1 3000 5 7000 µSv (700 mrem) in this
facility from the prep and scan FDG patients. Shielding
can be installed to decrease this amount significantly. As
an exercise, determining how much shielding would
need to be installed to reduce this technologist equivalent dose of 7000 µSv to a total of 1300 µSv (130 mrem)
per year or about 110 µSv/month (11 mrem/mo.) will be
discussed. The value used in this example is far below the
occupational annual maximum permissible dose (MPD)
of 0.05 Sv (5 rem). Fig. 16.3 depicts a facility layout sche-
matic that will be referred to for shielding calculations.
For simplicity, the calculations will not be for the entire
suite but will be limited to what is required for protection
of the PET-CT radiographer. In addition, the task will be
further confined to just the contributions from the patient occupying the prep room and the patient being
scanned. The hot lab and the patient’s toilet will have to
have their own substantial shielding installed to protect
other regular facility occupants and the general public.
Beginning with the scanned patient, let it be required
that both the technologist viewing window and the
x~midline of patient
PET/CT
scanner
(E) Corridor
Prep.
room
B
5 meters
7 meters
A
Hot
lab
PET
toilet
4 meters
(E) Corridor
D
Fig. 16.3 Layout diagram of a positron emission tomography/computed tomography (PET/CT) imaging facility.
CHAPTER 16 Radioisotopes and Radiation Protection
329
surrounding wall be shielded so that the 3000 µSv
(300 mrem) high-energy annual equivalent dose contribution from scan patients decreases to one-fourth of its
unshielded value, namely to 750 µSv (75 mrem). As mentioned earlier, the amount of lead needed to decrease the
intensity of this high-energy radiation by 50% (HVL) is
equal to 0.5 cm (approximately 0.2 inch) of lead. One
HVL will bring the equivalent dose down to 1500 µSv
(150 mrem), and two HVLs will decrease it to 750 µSv
(75 mrem). The two HVLs amount to installing: 2 3
(0.5 cm) of lead 5 1.0 cm (≈0.4 inches) of lead. This must
be placed in the wall surrounding the view window, and
the view window itself must be composed of the equivalent amount of lead acrylic. This thickness of lead is far
more than would be required to shield the operator from
the much less penetrating CT scatter radiation (typically
about 1/16” Pb). Therefore, the CT scatter radiation does
not have to be additionally accounted for. For the patient
in the prep room, the goal is to interpose enough shielding
so that the 4000 µSv (400 mrem) annual equivalent dose
contribution to the technologist location decreases to
500 µSv (50 mrem); this decrease by a factor of eight requires three HVLs, or 1.5 cm (0.59 inches) of lead. Examining the diagram, it is seen that this amount of shielding
can be distributed between the prep room corridor wall
and door (labeled A and D, respectively) and the scan suite
corridor wall (labeled B). Excluding personnel other than
the operator and discounting any other circumstances, a
practical solution is to place ½0 of lead in A and D and add
1/80 of lead in the portion of B necessary to shield the
technologist. This amounting to installing: 0.50 1 0.130 5
0.630 which is close enough to the calculated 0.590 Pb.
In conclusion, it is clear that there is much to be
considered when radiation shielding is designed for a
PET-CT facility. Other areas that are frequented by personnel and/or the general public must also be protected
from the high-energy radiation. Their protection involves lower permissible equivalent dose limits than for
the occupationally exposed radiographer. If there is the
opportunity to construct the facility from the beginning, then with an intelligent design the required shielding can be greatly reduced; if not, then the calculations
and the amount and variations of needed shielding can
be sizable.
RADIOIMMUNOTHERAPY (RIT)
In formal terms, RIT is a specific treatment protocol for
cancer by cytotoxic radioisotopes conjugated to specialized immune system antibodies. In the following, this
statement will be explained and explored in all of its
aspects. By no means, however, is the following meant
to be regarded as a complete presentation of this very
important and ongoing area of research.
The Immune System
Box 16.1 presents brief explanations of some of the
major organic entities involved in the operations and
reactions of the body’s immune system.
The body’s immune system is essentially an alliance
between cells and proteins that work together to provide defenses against infection. The immune system is
not a single organ but rather a collection of organs
dispersed throughout the body whose purpose is to
BOX 16.1 Organic Entities Involved in the Operations and Reactions of the Body’s Immune
System
Antigens are protein molecules that are not recognized by
the body and therefore seen as foreign by the immune
system, thereby stimulating the system’s production of
antibodies or immune cells.
Antibodies (Ab) are molecules produced by B-lympho-
cytes (white blood cells originating in bone marrow)
that circulate in the blood and will chemically bind
with and can interact destructively with antigens.
These are among the key agents of the body’s immune system.
A conjugate refers to a compound formed by the joining
of two or more chemical compounds.
A conjugated antibody (also known as a tagged, loaded,
or labeled antibody) is one that has been attached to a
substrate (the surface or material on or from which an
organism lives, grows, or obtains its nourishment) such
as an enzyme, toxin, or inorganic compound
Monoclonal antibodies (MABs or MoABs) are antibodies
that are made by identical immune cells that are all clones
of a unique parent cell. Thus, monoclonal antibodies are
cells derived by cell division from a single ancestral cell.
Pathogens are a bacterium, virus, or other microorganism
that can cause disease. A pathogen may also be referred to as an infectious agent, or simply a germ.
330
CHAPTER 16 Radioisotopes and Radiation Protection
provide rapid responses to foreign agents. It includes
organs such as the liver, thymus gland, bone marrow,
lymph nodes, spleen, and even the tonsils. The bone
marrow and thymus gland are important source locations for two key cells of the immune system called
B-cells and T-cells, respectively. Box 16.2 contains a
listing and description of the various cell types that
comprise the immune system. The development of all
cells of the immune system begins in the bone marrow
with a blood-forming “stem” cell. The name stem cell is
appropriate, since all of the other specialized cells arise
from it. Because of its ability to generate an entire immune system, this blood-forming cell is the cell that is
most important in a bone marrow or hematopoietic
cell transplant.
Although all components of the immune system interact with each other, it is typical to consider two broad
categories of immune responses: those originating with
BOX 16.2 Cells of the Immune System
Bone marrow: The site in the body where most of the
cells of the immune system are produced as immature
or stem cells.
Stem cells: These cells have the potential to differentiate
and mature into the different cells of the immune system.
Thymus: An organ located in the chest that instructs im-
mature lymphocytes to become mature T-lymphocytes.
Cytotoxic (killer) T-cells: These lymphocytes mature in
the thymus and are responsible for killing infected cells.
Helper T-cells: These specialized lymphocytes “help”
other T-cells and B-cells to perform their functions.
B-cells: These lymphocytes arise in the bone marrow and
differentiate into plasma cells that in turn produce immunoglobulins (antibodies).
Plasma B-cells: These cells develop from B-cells and are
the cells that make immunoglobulin for the serum and
the secretions.
Serum and plasma: Both come from the liquid portion of
the blood that is left over once the blood cells are removed. Serum is the liquid that remains after the blood
has clotted. Plasma is the liquid that remains when clotting
is prevented with the addition of an anticoagulant. Essentially, plasma is equal to serum minus clotting agent.
Immunoglobulins (Ig): These highly specialized protein
molecules, also known as antibodies, fit foreign antigens, such as polio, like a lock and key. Their variety is
so extensive that they can be produced to match all
possible microorganisms in our environment.
the innate immune system and those associated with the
adaptive immune system.
Innate immune responses rely on cells that require
no additional modifications to do their jobs. These cells
include neutrophils, natural killer (NK) cells, and a set of
proteins termed the complement proteins. Innate responses to infection occur rapidly and reliably. Even
infants have exceptional inherent immune responses.
Adaptive immune responses, however, involve T-cells
and B-cells, cell types that do require an “educational”
modification to prevent them from attacking harmless
cells. The advantages of the adaptive responses are their
long-lived memory and the ability to adjust to new
germs. Central to both categories of immune responses
is the ability to distinguish foreign invaders (things that
need to be attacked) from the body’s own tissues, which
of course need to be protected. Because of their ability
to respond rapidly, the innate responses are usually the
Immunoglobulin G (IgG): Representing approximately
75% of serum antibodies in humans, IgG is the most
common type of antibody found in blood circulation. IgG
molecules are created and released by plasma B-cells.
Neutrophils: A type of white blood cell (leukocytes) that
is one of the first cell types to travel to the site of an
infection. Neutrophils help fight infection by ingesting
microorganisms and releasing enzymes that kill the
microorganisms. Neutrophils are the most plentiful
type, making up 55% to 70% of your white blood
cells.
Complement proteins: The complement system is a
secondary part of the immune system produced in the
liver that enhances the ability of antibodies to clear microbes and damaged cells from an organism, promotes
inflammation, and attacks the pathogen’s cell membrane. It is essentially a “backup” complex system of
more than 30 proteins that, when triggered (caused to
be brought into play), act in concert to help eliminate
infectious microorganisms. Specifically, the comple-
ment system causes the bursting of foreign and infected cells and the ingestion of foreign particles.
Red blood cells: The cells in the blood stream that carry
oxygen from the lungs to the tissues.
Platelets: Small cells in the blood stream that are important
in blood clotting.
Dendritic cells: Important cells in presenting antigen to
immune system cells.
CHAPTER 16 Radioisotopes and Radiation Protection
331
first to react to an “invasion.” This initial response serves
to alert and trigger the adaptive response, which can
take several days to fully activate.
2
Monoclonal Antibodies
Monoclonal antibodies (MABs) are antibodies that
have monovalent affinity, which means simply that they
preferentially bind always to a specific part of an antigen
that is recognized by the antibody. To be more specific,
MABs work by identifying and locating specific proteins
on cells. Each MAB is attracted to one particular protein
of the many that are on the cell. Each works in different
ways depending on the foreign-appearing protein (antigen) they are targeting (Figs. 16.4 and 16.5).
Specifics of Radioimmunotherapy
RIT is a combination of radiation therapy and immunotherapy. In basic (i.e., non-RIT) immunotherapy, a labo-
ratory-produced specialized antibody is “engineered” to
recognize and bind to the surface of cancer cells. These
specialized antibodies mimic the antibodies naturally
produced by the body’s immune system that attack invading foreign substances, such as bacteria and viruses.
Radioimmunotherapy goes a step further and uses
such a specialized antibody that is also labeled or chemically combined with a radionuclide to deliver cytotoxic
(cell-killing) radiation to a target cell. Thus, for RIT cancer therapy, a radioactive antibody combination with
Cancer cell
Tumour-specific
MABs
Tumour-specific
antigens (TSA)
Fig. 16.4 Attack by the immune system on specific protrusions
of a cancer cell. (From Lilley, Harrington, Snyder: Pharmacology
for Canadian health care practice, ed 2, Milton, Ontario, 2011,
Elsevier Canada.)
Antigen
Epitope Epitope
Antibody Antibody
Fig. 16.5 Enlarged view of a “lock and key” interaction be-
tween an antibody and a protrusion of a cancer cell recognized
as a foreign protein or antigen by the immune system. (From
Worsfold P, Poole C, Townshend A, et al: Encyclopedia of ana-
lytical science, ed 3, Oxford, 2019, Elsevier Ltd.)
Antigen
specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The
ability of the antibody to preferentially bind (i.e., attach
itself) to a tumor-associated antigen increases the radiation dose delivered to the tumor cells while decreasing
the dose to normal tissues. By its nature, effective RIT,
ideally, requires a tumor cell to express or display an
antigen that is unique to the neoplasm or is not widely
accessible in normal cells. Otherwise, RIT would not be
practical. Thus, RIT is very dependent upon there being
made available and then using precise focused entities
such as monoclonal antibodies.
As an explicit example, an antibody known as an
immunoglobulin-G (IgG) is a large, Y-shaped protein
(shown in Figs. 16.4 and 16.5), produced mainly by
plasma cells, that is employed by the immune system to
neutralize germs such as pathogenic bacteria and viruses. IgG is sensitive to a unique molecule or antigen
of the pathogen. Each tip of the “Y” of an antibody
contains a paratope (analogous to a lock, a paratope is a
part of an antibody that recognizes and binds to an
antigen) that is specific for one particular structure
(similar to a key) on an antigen, allowing these two
structures to join together with precision (see Fig. 16.5).
Using this binding mechanism, an antibody can mark a
microbe or an infected cell for attack by other parts of
the immune system, or can neutralize its target directly
332
CHAPTER 16 Radioisotopes and Radiation Protection
(for example, by inhibiting a part of a microbe that is
essential for its invasion and survival). Cancer cells
naturally produce cancer-associated biological molecules, which are adaptive features of malignant change
that possess multiple foreign-appearing (antigenic)
binding sites in relatively high abundance in comparison to normal tissues.
As mentioned before, in RIT a radioactive isotope
(typically a short-range, high-energy beta emitter) is
chemically bound to a target-specific monoclonal antibody forming a radioactive conjugate or team that combines the excellent targeting specificity of the immune
system with the known cancer-killing power of high
energy radiotherapy. These radioantibodies are introduced into the blood or into a body cavity, such as the
peritoneum, pleura, or intrathecal space,* and are subsequently carried to the antigen-binding sites or targets
on the tumor cells by blood flow, diffusion, or the
wholesale flow of fluid. Thus, when injected into the
bloodstream, appropriate radionuclide-linked monoclonal antibodies travel to and bind to cancer cells, cumulatively causing a high dose of destructive radiation
to be delivered directly to the tumor cells while at the
same time limiting radiation effects on neighboring
healthy cells. Systemic radiotherapy with radiolabeled
immunoconjugates delivers a non-uniform, low-dose
rate irradiation over a prolonged period of time, in contrast to external beam radiotherapy, which is usually
engaged for only minutes at a time. RIT thus far has
been more successful in hematological cancers than in
solid tumors.
Agents of RIT and Their Destructive Capabilities
Radioimmunotherapy drugs that rely upon an alpha
particle-emitting isotope (e.g., Bismuth-213 or Actinium-225), rather than a beta emitter, as the killing source
of radiation tend to be more effective. The most developed drug in this category thus far is directed toward
treating acute myeloid leukemia (AML).** Other types
of cancer for which RIT has therapeutic potential include
prostate cancer, metastatic melanoma, ovarian cancer,
*Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected
into the fluid or a sample of the fluid.
various types of leukemia, and high-grade brain tumors.
Table 16.1 provides a list of some radioisotopes used or
considered for RIT.
Irradiated cells absorb substantial amounts of energy
in the form of photons or charged particles, which promote both direct macromolecular harmful alterations
as well as indirect damage due to the generation of reactive oxygen and/or nitrogen species (free radicals, etc.
See Chapter 7 for a detailed discussion of irradiationinduced molecular changes). Both free radicals and
molecular oxygen can alter DNA strands, and the damage induces not only the onset of apoptosis (programmed cell death) but also significant necrosis (the
death of most or all of the cells in an organ or tissue due
to disease, injury, or failure of the blood supply).
For minimizing collateral injury of nearby normal
cells from the radiation used for therapy, alpha particle
or short-range beta particle emitters are preferable.
There have also become available some MABs that are
**Acute myeloid leukemia (AML) is a cancer of the blood and
bone marrow. It is a type of cancer in which the spongy tissue
of the bone marrow makes abnormal myeloblasts (a type of
white blood cell), red blood cells, or platelets.
TABLE 16.1 Some Radioisotopes Used
and Considered for RIT
Radioisotope Energy (MeV) Range Half-life
Beta-particle emitters
67
Copper 0.58 2.1 mm 2.6 d
90
Yittrium 2.28 12.0 mm 2.7 d
131
Iodine 0.61 2.0 mm 8.0 d
186
Rhenium 1.07 4.5 mm 3.7 d
188
Rhenium 2.12 10.4 mm 16.9 hr
Alpha-particle emitters
211
Astatine 6.8 80 µm 7.2 hr
213
Bismuth 8.3 84 µm 46 min
225
Actinium 6.0,8.0 60,90 µm 10.0 d
Auger-electron emitter
125
Iodine varied 2,500 nm 59.5 d
Data from Kawashima H: Radioimmunotherapy: a specific
treatment protocol for cancer by cytotoxic radioisotopes
conjugated to antibodies, Sci World J vol. 2014, 2014.
doi 10.1155/2014/492061.
CHAPTER 16 Radioisotopes and Radiation Protection
333
coupled with radioisotopes that emit very short-range
Auger electrons (see Chapter 3). Table 16.1 shows some
of the radioisotopes that have been or may be utilized
for RIT.
Because an alpha particle gives its energy to the
surrounding molecules within a very narrow range
(,100 mm, equivalent to a few cell diameters), it leads
to a much more concentrated energy transfer within
the target and therefore less collateral effect to nontarget tissues as compared to antibodies labeled with
beta emitters. In addition to an alpha particle’s very
high linear energy transfer (LET), which results in
a large relative biological effectiveness (RBE), the
cytotoxic (cell-killing) efficacy of an alpha particle is
independent of the local oxygen concentration and cell
cycle state.
The success of RIT depends on the selective accumulation of cytotoxic radioisotopes at affected areas.
Fundamental properties required for effective agents
against a particular bio target are: (1) high binding affinity to the intended mark, (2) high specificity, (3)
high metabolic stability, and (4) low body self-rejection
or immunogenicity.* From the viewpoint of those molecular characteristics, MABs have been regarded as
very suitable vehicles for the delivery of therapeutic
radioisotopes.
One of the most intriguing advantages of RIT over
external x-ray beam radiotherapy is the ability to attack
not only the primary tumor but also lesions systemically metastasizing or spreading. Thus, targeted radiotherapy treatments using specific vehicle agents can
be effective in cases of (1) residual micrometastatic
lesions, (2) residual tumor margins after surgical
resection, (3) tumors in the circulating blood including
*Today, “biologic” drugs provide more treatment options
for various diseases. But even these newer drugs have flaws,
because in a small percentage of patients, there is a self-immune
response to the drug
compromised. That undesirable response is called “immunogenicity.” The challenge for researchers is to develop biologic
drugs that don’t provoke that kind of self-immune response, so
that all patients can be treated with these medicines. Currently,
it is difficult or impossible for physicians to predict which
patients are going to end up with an immunogenic response,
which makes it tricky to monitor them and prescribe the right
treatment.
3
, and so its effectiveness over time may be
hematologic malignancy, and (4) malignancies that
present as free-floating cells. Certain types of cancer,
therefore, which are not well handled by conventional
means (i.e., external x-ray irradiation and/or chemotherapy), may well have much better potential probabilities for resolution with RIT.
4
How RIT Is Performed
A nuclear medicine physician and a radiation oncologist and other health care professionals, such as a
medical physicist, a nuclear medicine technologist,
and an oncology nurse, usually make up the team involved in RIT procedures. In general, a patient will receive a treatment either by an injection under the skin
(subcutaneous injection) or through a drip (infusion)
into a vein. RIT usually consists of several such procedures. For some drugs the first treatment will be into a
vein, and then remaining treatments will be delivered
subcutaneously. In either way, the “radioantibody” is
introduced into the blood or a body cavity such as the
peritoneum, pleura, or intrathecal space, and from there
it is carried to its natural target or antigen-binding site
on the tumor cell by blood flow, diffusion, or the bulk
flow of fluid.
In general, for the patient, the most serious and most
common side effect of RIT therapy is a decrease in
blood counts due to various degrees of unavoidable collateral damage. This side effect may be present as late as
several months after treatment but can be medically
managed.
Radiation Safety Considerations
Because there are multiple drug-radionuclide combinations that have been used or are in test trials (all of
which have alpha or beta or gamma emissions or
some combinations thereof), it is therefore practical
for this text’s educational purposes to just consider,
as an example, the radiation safety and dosimetry
characteristics of one of the most commonly used
combinations, namely beta-emitter Yittrium-90 (Y90)*
*Y90 Characteristics: pure beta emitter, decay energy 0.94 MeV,
maximum range in tissue 11 mm (2.5 mm average), T
64.2 hours. Two production methods: (1) Nuclear Reactor, (2)
Sr90 / 39Y90 generator [Note: 38Sr90 (Strontium-90) decays by
38
beta decay into 39Y90, which then undergoes beta decay itself
yielding an isotope of Zirconium 40Zr90].
1/2 5
334
CHAPTER 16 Radioisotopes and Radiation Protection
microspheres, ** which are chemically bonded to im-
munoglobulin G (IgG). Representing approximately
75% of blood plasma antibodies in humans, IgG is the
most common type of antibody found in the blood
circulation. IgG molecules are created and released by
plasma B cells (see Box 16.2).
A practical and efficient agent for the above mixture is
Yttrium-90 joined with the immunoglobulin Ibritumomab Tiuxetan (trade-name Zevalin). For Zevalin,
other than acrylic shielding around the syringe, only
standard universal precautions for personnel are required
to administer the drug, and strict patient isolation is
unnecessary because of the significant self-absorption of
the emitted radiation by the patient’s body in general.
After the radiolabeled antibodies bind to receptors/
tumor antigens expressed on the surface of cancerous
tissue, cells within an anatomic region reached by the
radioactive emissions (beta particles in the case of Y90)
will be killed.
RIT with Zevalin is currently most often used to treat
non-Hodgkin B-cell lymphoma*** (NHL) for newly
diagnosed patients and for patients who have not responded to chemotherapy procedures.
5
Patients who have had prior bone marrow transplantation or failed stem cell collection should not receive
RIT. Y90-microsphere treatment is a multiple interdisciplinary treatment modality. Treatment planning and
execution can jointly involve interventional radiology,
radiation oncology, and nuclear medicine. Microbrachy-
**A microsphere is a spherical shell that is usually made of a
biodegradable or resorbable plastic polymer, that has a very
small diameter, customarily in the micron or nanometer
range, and that is often filled with a substance (such as a drug
or antibody or radionuclide conjugated to an antibody) for
release as the shell is degraded.
***Both Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
are types of cancer that begin in a subset of white blood cells
(lymphocytes). Lymphoma can develop when lymphocytes
(white blood cells that fight infection) grow out of control.
This is brought about by genetic changes in the cells that cause
them to no longer “listen” to signals that control their growth
and death. The main difference between Hodgkin’s lymphoma
and non-Hodgkin’s lymphoma is in the specific lymphocyte
each involves. If in examining the cells under a microscope
there is detected the presence of a specific type of abnormal
cell called a Reed-Sternberg cell (large multi-nucleus cells), the
lymphoma is classified as Hodgkin’s.
therapy, a term used by radiation oncologists, originates
from the approval of Y90 microspheres by the US Food
and Drug Administration (FDA) as medical devices.
The actual use of Y90 microspheres, however, is as a
radiopharmaceutical. The material is prepared in a
solution and its activity is assayed in a nuclear medicine
dose calibrator. The treatment prescription is specified
in units of activity (typically gigabecquerels (GBq) or
mCi). Absorbed dose to the tumor target is not used in
the treatment prescription. The agent is administered
by use of a syringe or injector via a catheter into an
artery. For Zevalin, there is, however, some radiation
that is detectable outside of the patient’s body, which
can lead to exposures of others at close distances. It
is caused by an escaping bremsstrahlung radiation
component due to high-energy electrons interacting
with larger-atomic-number materials in the patient,
such as bone. Consequently, it is recommended that
treated patients generally maintain at least a 1 meter
distance from others, especially young children and
pregnant women for over a week (multiple half-lives
of Y90) after application of Zevalin. Furthermore, the
beta radiation component, almost entirely absorbed
by the body, can, however, in the case of a nursing
mother via breast milk ingestion compromise a nursing
infant, and consequently nursing should cease for at
least five half-lives of Y90 (about 2 weeks). Microspheres
typically measure between 20 and 30 microns in
diameter and are infused with Y90 at a specific activity
of 2400 to 2700 Bq per sphere. Typical total treatment
activities are in the range of 2 to 6 GBq (approximately
50 to 160 mCi).*
Y90 microsphere therapy is regulated by the Nuclear
Regulatory Commission (NRC), pursuant to 10 CFR
35.1000, and patient release must follow the requirements in 10 CFR 35.75. A licensee may release patients,
regardless of administered activity to that patient, if it
can be demonstrated that the total effective dose equiva-
lent (TEDE) to another individual from exposure to a
released patient is not likely to exceed 5 mSv (0.5 rem).
In addition, pursuant to 10 CFR part 35.75(b), licensees
must provide a released patient with written instructions
on actions recommended to maintain ALARA doses to
*1 GBq 5 109 disintegrations per second (dps). This is equivalent to 27 millicuries since 1 mCi 5 3.7(10)7 dps.
CHAPTER 16 Radioisotopes and Radiation Protection
335
other individuals if the dose to any other individual is
likely to exceed 1 mSv.
For radiation safety regulatory purposes, only the
bremsstrahlung radiation component is considered
here, because the involved direct beta dose would be
negligible. The following empirical equation can be
used to estimate the total dose that an individual is
likely to receive from exposure to a released patient at a
distance r measured in centimeters:
∞∞
DDEE(( )) ((3344..66 AA TT OOFF))// rr **
ΓΓ 5
pp
22
where in this equation: DE () is external exposure dose
equivalent, attributable to bremsstrahlung radiation, up
to total decay (i.e., out to infinite time) in mSv; is the
specific bremsstrahlung equivalent dose rate constant**
for Y90 in soft tissue equal to 1.52 3 10-3 mSv/cm2/MBq/
hr at 1 cm; A is the administered activity in megabecquerels (MBq); Tp is the physical half-life of the radionuclide
in days (2.67 days for Y90); OF is the assumed practical
occupancy factor at 100 cm (0.25); and r is distance from
the patient in centimeters.
6
This equation can be used to calculate a projected
potential TEDE to a family member who for a quarter
of the time of the implant duration maintains a distance
of 1 m from a patient who has received a treatment dosage of 6 GBq (162 mCi). The family member is assumed
*The equation can be considered to be an approximation because it was derived under the idealized assumptions of instantaneous patient activity uptake, uniform activity deposition through the patient, and no biologic elimination. It can
be solved for the maximum allowable administered activity
for authorizing patient release on the basis of the 5 mSv (500
mrem) regulatory dose limit. In compliance with the public
dose limit in 10 CFR 35.75(a), licensees may release patients
from their control if the activity administered to each treated
patient is no greater than 1420 GBq. Patient instructions are
required only if the dose to other individuals is likely to exceed
1 mSv (0.1 rem). This dose equivalent would correspond to
one-fifth of the maximum allowable release value, corresponding to an administered activity of 284 GBq. Since all
patients treated with 90Y-microspheres receive a treatment
activity that is enormously lower than this value, all such patients can be released; no records or instructions are required
by the NRC.
**An experimentally determined value based upon the mean
bremsstrahlung energy.
7,8
to spend negligible time closer to the patient than 100
cm. Substituting into the equation the various parameter values yields:
3
TEDE (family member) 34. 6 1.52(10)
6000 2.67 0.25/(100)
2
5 0.022 mSv (2.2 mrem)
Although the 6 GBq or 162 mCi dosage is greater
than the normal Y90 dosage used (see below), it is seen
to produce a TEDE to an informed family member that
is substantially below the NRC regulatory limit.
Because of calculations such as the above and associated radiation protection survey results, it is well recognized that Y-90 Zevalin therapy can be safely done on an
outpatient basis using only standard universal precautions. The typically administered dose of Y-90 Zevalin is
between 777 and 1110 MBq (21 to 30 mCi), with a
maximum of 1184 MBq (1.184 GBq or 32 mCi).
Imaging for RIT Proper Treatment Delivery
The therapy aspect of RIT is usually coupled with a
Nuclear Medicine imaging component to ascertain the
actual targeting efficacy of the monoclonal antibody
employed. Nuclear Medicine scanners cannot image the
actual radioactive distribution of an agent from beta or
alpha emissions because those radiations are absorbed
locally to such a high degree that there is a negligible
external signal for a Nuclear Medicine camera* to detect. Instead, a pretreatment dose of pharmaceutical in
which the MABs are tagged with technetium Tc
(which emits easily detectable 140 keV gammas) is administered and thereby generates, an image of the biological distribution of that pharmaceutical. Based upon
the biodistribution seen in the technetium image, the
amount of radionuclide (such as the beta emitter Y90) to
be injected into the patient is selected so as to deliver a
*Nuclear Medicine camera, also called a scintillation camera, it
is an energy-selective device used mainly to image gamma radiation emitting radioisotopes. It precisely records the distribution of radiation emitted from a chemical compound containing a radionuclide that is attracted to specific organs or
tissues and thereby can be used to quantitatively ascertain the
amount of radionuclide taken up by various scanned regions
of interest.
99m
336
CHAPTER 16 Radioisotopes and Radiation Protection
tumoricidal dose that will not cause unacceptable harm
to healthy tissues (Fig. 16.6).
Summary of RIT
RIT, although not a general treatment modality, has, for
its specific effective applications, unique advantageous
properties:
• It takes about 1 week to deliver regions of interest
(ROIs), shown in red in Fig. 16.6, as compared to
many months for chemotherapy.
• It is the only non-chemotherapy-based approach
with a good rate of durable remissions.
• It is an important choice for patients:
• who must continue to work through or shortly
after treatment
• who cannot tolerate chemotherapy, because of
advanced age, or specific coexisting other ailments.
• who may be insistent on limiting the on-
treatment side effects specific to chemotherapy
LUNG
LUNG
LIVER
Fig. 16.6 Injected 99mTc-serum albumin labeled antibody distri-
bution activity in liver and lung in a patient with liver carcinoma.
ROIs (regions of interest) outlined in red around lungs and liver
demonstrate respective number of organ counts, which, for a
calibrated imaging technique can be translated into a quantitative estimate of the likely distribution of an alpha particle emitting radiopharmaceutical to be administered later for therapeutic
purposes. Serum albumin is the main protein component of
human blood plasma. (From Jadvar H: Targeted Radionuclide
therapy: an evolution toward precision cancer treatment, AmJ
Roentgenol, 209:277–288, 2017, ©SNMMI. This research was
originally published in the Journal of Nuclear Medicine.)
544363 cts.
LIVER
1937144 cts.
such as nausea, neuropathy, hair loss, and gastric
and mucositis complications.
A significant disadvantage, however, is the very high
cost, in excess of $30,000, of receiving a RIT treatment. In
addition, as was mentioned before, it is not currently
available for a variety of solid tumors (e.g., rectal cancer).
RADIATION EMERGENCIES: USE OF RADIATION AS A TERRORIST WEAPON
After the attack on the World Trade Center by hijacked
airplanes on September 11, 2001, the possibility of the
use of other terrorist weapons, such as radiation, became
a public health concern. Today, most hospitals have
elaborate crisis plans for handling emergency situations
involving radioactive contamination. Radiologic technologists should become aware of the radiation emergency plans that exist in the facilities in which they work.
In this section, some fundamental principles of dealing
with radioactive contamination in a health care environment are discussed.
Contamination
A radioactive dispersal device, or “dirty bomb,” is a
radioactive source mixed with conventional explosives.
It is intended to contaminate an area with radioactive
material and thereby cause panic. The actual long-term
health effects of a dirty bomb are likely to be minimal.
If the radioactive material remains in a small area, few
people may be affected. However, if enough explosives
are used to spread the radioactive material over a broad
area, then the radioactivity will be diluted and may not
be much higher than background levels.
For example, it would be difficult for terrorists to
accumulate as much radioactive material as existed in
the Chernobyl nuclear reactor. Even if they were able
to do this and were to explode the device with the
same force as the explosion at Chernobyl, the actual
number of radiation injuries would probably be quite
small. At Chernobyl, no cases of acute radiation syndrome (ARS) were caused by exposure outside the
immediate vicinity of the reactor. The only cases occurred in emergency workers, primarily firemen, who
worked very near the reactor. They had little training
and essentially no protective gear to prepare them for
a radioactive emergency. In the United States at the
present time, emergency responders are equipped to
monitor and assess personnel exposure on-site.