Radiopharmaceuticals are used in nuclear medicine for imaging and therapy and it is proving to be highly effective.

3.  A radiopharmaceutical is a radioactive compound
used for the diagnosis and therapeutic treatment of
human diseases.
 In nuclear medicine nearly 95% of the
radiopharmaceuticals are used for diagnostic
purposes, while the rest are used for therapeutic
treatment.
 Radiopharmaceuticals usually have minimal
pharmacologic e¤ect, because in most cases they
are used in tracer quantities.
 Therapeutic radiopharmaceuticals can cause tissue
damage by radiation.

4.  Because they are administered to humans,
they should be sterile and pyrogen free,
and should undergo all quality control
measures required of a conventional drug.
 A radiopharmaceutical may be a
radioactive element such as 133Xe, or a
labeled compound such as 131I-iodinated
proteins and 99mTc-labeled compounds.

5.  Although the term radiopharmaceutical is
most commonly used, other terms such as
radiotracer, radiodiagnostic agent, and
tracer have been used by various groups.
 We shall use the term
radiopharmaceutical throughout, although
the term tracer will be used occasionally.

6.  Another point of interest is the difference
between radiochemicals and
radiopharmaceuticals.
 The former are not usable for administration
to humans due to the possible lack of
sterility and nonpyrogenicity.
 On the other hand, radiopharmaceuticals
are sterile and nonpyrogenic and can be
administered safely to humans.

7.  A radiopharmaceutical has two
components:
a radionuclide and a pharmaceutical.
 The usefulness of a radiopharmaceutical is
dictated by the characteristics of these two
components.
 In designing a radiopharmaceutical, a
pharmaceutical is first chosen on the basis
of its preferential localization in a given
organ or its participation in the physiologic
function of the organ.

8.  Then a suitable radionuclide is tagged onto
the chosen pharmaceutical such that after
administration of the radiopharmaceutical,
radiations emitted from it are detected by
a radiation detector.
 Thus, the morphologic structure or the
physiologic function of the organ can be
assessed. The pharmaceutical of choice
should be safe and nontoxic for human
administration.

9.  Radiations from the radionuclide of
choice should be easily detected by
nuclear instruments,and the radiation
dose to the patient should be minimal.

11.  Since radiopharmaceuticals are
administered to humans, and because
there are several limitations on the
detection of radiations by currently
available instruments,
radiopharmaceuticals should possess some
important characteristics.
 The ideal characteristics for
radiopharmaceuticals are:

12. 1. Easy Availability
 The radiopharmaceutical should be easily
produced, inexpensive, and readily available
in any nuclear medicine facility
 Complicated methods of production of
radionuclides or labeled compounds increase
the cost of the radiopharmaceutical.
 The geographic distance between the user
and the supplier also limits the availability of
short-lived radiopharmaceuticals.

13. 2. Short Effective Half-Life
 A radionuclide decays with a definite half-life,
which is called the physical half-life, denoted
Tp (or t1=2).
 The physical half-life is independent of any
physicochemical condition and is
characteristic for a given radionuclide

14. 2. Short Effective Half-Life (cont,..)
 Radiopharmaceuticals administered to humans
disappear from the biological system through fecal
or urinary excretion, perspiration, or other
mechanisms.
 This biologic disappearance of a
radiopharmaceutical follows an exponential law
similar to that of radionuclide decay.
 Thus, every radiopharmaceutical has a biologic
half-life (Tb).
 It is the time needed for half of the
radiopharmaceutical to disappear from the
biologic system and therefore is related to a decay
constant= 0.693/λ= TP

15. 2. Short Effective Half-Life (cont,..)
 Obviously, in any biologic system, the loss of a
radiopharmaceutical is due to both the
physical decay of the radionuclide and the
biologic elimination of the
radiopharmaceutical.

16. 3. Particle Emission
 Radionuclides decaying by a- or b-particle
emission should not be used as the label in
diagnostic radiopharmaceuticals.
 These particles cause more radiation damage
to the tissue than do g rays.
 Although g-ray emission is preferable, many b-
emitting radionuclides, such as 131I-iodinated
compounds, are often used for clinical studies.

17. 3. Particle Emission (cont,..)
 However, a emitters should never be used for in
vivo diagnostic studies because they give a
high radiation dose to the patient.
 But a and b emitters are useful for therapy,
because of the effective radiation damage to
abnormal cells.

18. 4. Decay by Electron Capture or Isomeric
Transition
 Because radionuclides emitting particles are
less desirable, the diagnostic radionuclides
used should decay by electron capture or
isomeric transition without any internal
conversion.
 Whatever the mode of decay, for diagnostic
studies the radionuclide must emit a Ɣ radiation
with an energy preferably between 30 and 300
keV. Below 30 keV, Ɣ rays are absorbed by
tissue

19.  Photon interaction in the NaI(T1) detector using
collimators. A 30-keV photon is absorbed by the
tissue. A> 300-keV photon may penetrate
through the collimator septa and strike the
detector, or may escape the detector without
any interaction.
 Photons of 30 to 300 keV may escape the organ
of the body, pass through the collimator holes,
and interact with the detector.

20. 4. Decay by Electron Capture or Isomeric Transition (cont,..)
 and are not detected by the NaI(Tl) detector.
 Above 300 keV, e¤ective collimation of g rays cannot be
achieved with commonly available collimators.
 However, recently manufacturers have made
collimators for 511-keV photons, which have been used
for planar or SPECT imaging using 18FFDG.
 The phenomenon of collimation with 30- to 300-keV
photons is illustrated
 approximately 150 keV, which is most suitable for
present-day collimators.
 Moreover, the photon abundance should be high so
that imaging time can be minimized due to the high
photon flux.

21. 5. High Target-to-Nontarget Activity Ratio
 For any diagnostic study, it is desirable that the
radiopharmaceutical be localized
preferentially in the organ under study since
the activity from nontarget areas can obscure
the structural details of the picture of the target
organ.
 Therefore, the target-to-nontarget activity ratio
should be large.

22. 5. High Target-to-Nontarget Activity Ratio (cont,..)
 An ideal radiopharmaceutical should have all
the above characteristics to provide maximum
effcacy in the diagnosis of diseases and a
minimum radiation dose to the patient.
 However, it is diffcult for a given
radiopharmaceutical to meet all these criteria
and the one of choice is the best of many
compromises.

24.  Many radiopharmaceuticals are used for various nuclear
medicine tests.
 Some of them meet most of the requirements for the
intended test andtherefore need no replacement.
 For example, 99mTc–methylene diphosphonate (MDP) is an
excellent bone imaging agent and the nuclear medicine
community is fairly satisfied with this agent such that no
further research and development is being pursued for
replacing 99mTc-MDP with a new radiopharmaceutical.

25.  However, there are a number of other radio
pharmaceutical that offer only minimal
diagnostic value in nuclear medicine tests
and thus need replacement.
 Continual effort is being made to improve or
replace such radiopharmaceuticals.

26.  Upon scrutiny, it is noted that the commonly
used radiopharmaceuticals involve one or
more of the following mechanisms of
localization in a given organ:
1. Passive diffusion: 99mTc-DTPA in brain imaging,
99mTc-DTPA aerosol and 133Xe in ventilation
imaging, 111In-DTPA in cisternography.
2. Ion exchange: uptake of 99mTc-phosphonate
complexes in bone.

27. 3. Capillary blockage: 99mTc macro-aggregated
albumin (MAA) particles trapped in the lung
capillaries.
4. Phagocytosis: removal of 99mTc-sulfur colloid
particles by the reticuloendothelial cells in the liver,
spleen, and bone marrow.
5. Active transport: 131I uptake in the thyroid, 201Tl
uptake in the myocardium.
6. Cell sequestration: sequestration of heat-damaged
99mTc-labeled red blood cells by the spleen.

28. 7. Metabolism: 18F-FDG uptake in myocardial and brain
tissues.
8. Receptor binding: 11C-dopamine binding to the
dopamine receptors in the brain.
9. Compartmental localization: 99mTc-labeled red blood
cells used in the gated blood pool study.
10. Antigen-antibody complex formation: 131I-, 111In-, and
99mTc-labeled antibody to localize tumors.
11. Chemotaxis: 111In-labeled leukocytes to localize
infections.

29.  Based on these criteria, it is conceivable to
design a radiopharmaceutical to evaluate
the function and/or structure of an organ of
interest.
 Once a radiopharmaceutical is
conceptually designed, a definite protocol
should be developed based on the
physicochemical properties of the basic
ingredients to prepare the
radiopharmaceutical.

30.  The method of preparation should be
simple, easy, and reproducible, and should
not alter the desired property of the labeled
compound.
 Optimum conditions of temperature, pH,
ionic strength, and molar ratios should be
established and maintained for maximum
effcacy of the radiopharmaceutical.

31.  Once a radiopharmaceutical is developed and
successfully formulated, its clinical effcacy must be
evaluated by testing it first in animals and then in
humans.
 For use in humans, one has to have a Notice of
Claimed Investigational Exemption for a New Drug
(IND) from the U.S. Food and Drug Administration
(FDA), which regulates the human trials of drugs
very strictly.
 If there is any severe adverse e¤ect in humans due
to the administration of a radiopharmaceutical,
then the radiopharmaceutical is discarded.