1711710 - Lecture 1+2. 2025.pdf.pua.mig.rad

radionuclide

1. Radiopharmaceuticals
Dr. Hend Aly
1711710 –Fall 2025 –Lecture 1+2

2. •Nuclear medicine is a rapidly growing, interdisciplinary field
based on the use of radioactive nuclides for diagnostic and
therapeutic purposes.
•The development of radiopharmaceuticals is a key aspect of
expanding the clinical capabilities of nuclear medicine physicians
and is achieved by continually improving the existing framework
of current drug design.
2

3. Radiopharmaceutical
•Any medicinal product which, when ready
for use, contains one or more radionuclides
(radioactive isotopes) included for a
diagnostic or therapeutic purpose.
•A radiopharmaceutical has two
components:
•a radionuclide and a pharmaceutical.
•The usefulness of a radiopharmaceutical
is dictated by the characteristics of these
two components.
3

4. •In designing a radiopharmaceutical:
•A pharmaceutical is first chosen based on its preferential
localization in a given organ or its participation in the
physiologic function of the organ.
•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.
4

5. Clinical translation of radiopharmaceuticals
5

6. 6

7. 7

8. Clinical translation of radiopharmaceuticals:
•The development of a radiopharmaceutical requires many steps to finally be
available for clinical use as a medicinal product, starting from the production of
the radionuclide and precursor (vector), then radiochemical development to the
biological characterization, pharmaceutical formulation and human studies
within clinical trials.
•Data need to be generated regarding the chemical and pharmaceutical quality
“Quality data”, but also data to predict safety and efficacy before human
applications.
•These non-clinical data cover pharmacology, radiation effects and
toxicology.
8

9. 9

10. Radiopharmaceutical
•Radiopharmaceuticalsareradiolabeledmoleculesdesignedforinvivo
application.
•Routeofadministrationcouldbeby
•Inhalation
•Oral
•Intravenous
•InterstitialRoute
10

11. Radiochemical Radiopharmaceutical
•Therearemanysimilaritiesbetweenthem.
•Fromthestandpointofbothchemistryandradionuclidepurity,thereis
usuallyminimalornodifference.
VS
11

12. Radiochemical Radiopharmaceutical
•It typically doesn't undergo this rigorous
testing and neither their sterility nor
apyrogenicity is guaranteed.
•It is not an FDA-approved agent for routine
human use.
•Radiochemical usage is usually limited to
chemical and biological research; in
addition, the tracers used in
radioimmunoassay (RIA) procedures are
usually radiochemical grade.
•It undergone a very lengthy and expensive regulatory
process as well as extensive chemical and physical
testing (pH, isotonicity, and chemical parameters) to
ensure that the final product is sterile, pyrogen-free,
safe for human use, and is efficacious for a specific
indication.
•Approved as radioactive drugs or
radiopharmaceuticals by the US Food and Drug
Administration (FDA).
•This includes both animal and human studies prior
to release of the product for sale.
•Radiopharmaceuticals are designed for clinical usage.
•but may serve as tracers in research projects.
12

13. Radionuclide VsRadiopharmaceutical VsRadiotracer
•Radionucliderefers to a physically-defined
radioactive atom (nuclide) of a particular element and
does not define its chemical state nor its intended use.
13

14. Radionuclide VsRadiopharmaceutical VsRadiotracer
•Radiopharmaceuticaldefines a radioactive
preparation for medical in vivo application which
meets all the standards set for non-radioactive
pharmaceuticals.
14

15. Radionuclide VsRadiopharmaceutical VsRadiotracer
•Radiotracerdenotes any radioactive material
which can be used to trace an entity or a
phenomenon within a more complex medium.
15

16. •The terms, radiotracer, radioligand, and radiodiagnostic
agent each have specific meaning depending on their
clinical context.
•From a regulatory point of view, the term radiopharmaceutical
represents any radiolabeled molecule intended for human use.
16

17. Radiopharmaceuticals
Usages
•In nuclear medicine nearly 90% of the
radiopharmaceuticals are used for diagnostic
purposes, while the rest are used for therapeutic
treatment.
•Therapeutic radiopharmaceuticals can cause tissue
damage by radiation.
17

18. 18

19. •Diagnostic radiopharmaceuticals emit or indirectly produce photons,
which are detected by high-density material to produce spatial
representations of drug distribution in vivo.
•Positron-emission tomography (PET) and single-photon emission
computed tomography (SPECT) are the most prevalent imaging
modalities for this purpose.
•PET: is based on the detection of 2 γ-rays, with a characteristic energy of
511 keV, emitted from positron (β+ ) emitters annihilation with electrons
(β−).
•SPECT: two-dimensional scintigraphy, SPECT is based on the detection of
γ-rays emitted from radiotracers, often as a result of electron capture (EC)
or isomeric transition (IT).
19

20. •Since radiopharmaceuticals are chemically indistinguishable from their non-
radioactive counterparts the organism does not make a difference in using the
radiolabeled derivatives as surrogates in all its biochemical processes.
•Thus, radiopharmaceuticals can be used to directly visualize these functional
processes in vivo.
•If, for example, there is a pathological change on the molecular level
resulting in abnormal function it can probably be visualized long before
morphological manifestation.
20

21. 21

22. 22

23. •Therapeuticradiopharmaceuticalsprimarily induce their cytotoxic effects
through irreversible DNA damage, resulting in deletions, chromosome aberrations,
and cell death.
•DNA damage can be achieved with the emission of beta (β−) particles, alpha (α)
particles, or low-energy electrons (henceforth, Auger electrons).
•The ability of an emitted particle to damage DNA is heavily dependent on its linear
energy transfer (LET), which is a measure of atom ionization/excitation per unit
length and is commonly reported in keV/μm for biological systems.
•High LET is typical of highly ionizing radiation and signifies dense energy
deposition. Particles with high LET deposit their energy over shorter distances than
those with low LET and are more effective at causing biological and/or chemical
damage.
23

24. 24

25. 25

26. Tissue range is dependent on both a
particle’s LET and kinetic energy.
•When particles have identical energy but
different LET, the particle with higher LET
will deposit its energy more rapidly, resulting
in shorter tissue range.
•Long tissue range can be useful for treatment of
large tumors.
•But it is increasingly regarded as
undesirable because it is directly linked to
off-target toxicity.
•Auger electrons are the least explored
therapeutic.
26

27. •Theranosticradiopharmaceuticals:
•Combined therapeutic and diagnostic (“theranostic”) isotopes are an
emerging concept and are desirable because of their ability to diagnose,
treat, and evaluate treatment, simultaneously or following a therapeutic
regimen.
27

28. •Theranostics in nuclear medicine, or nuclear theranostics, refers
to the use of radioactive compounds to image biologic
phenomena by means of expression of specific disease targets
such as cell surface receptors or membrane transporters, and then
to use specifically designed agents to deliver ionizing radiation to
the tissues that express these targets.
•Diagnostic radioisotope to perform initial low dose imaging
to evaluate biodistribution and clearance.
•Therapeutic radionuclide to achieve individual therapies.
28

29. 29

30. Matched pairs
The diagnostic and therapeutic radionuclides
belong to one and the same chemical
element.
30

31. •The simultaneous
emission of imageable
gamma photons along
with particulate β(-)
emission makes Lu-177 a
theranostically desirable
radioisotope.
Some radionuclides are inherently theranostic, generally by virtue of a
therapeutic nuclide having an imageable γ-line (e.g.,
47
Sc,
177
Lu).
31

32. •The most ideal theranostic agents are composed of chemically identical
radioisotope pairs with similar half-lives and complementary emission.
•In this way, the diagnostic and therapeutic decay modes are optimal (i.e., high
branching and appropriate energy) and the radioisotopes exhibit identical
(bio)chemical behavior, notably with respect to the chelator.
•This ensures the therapeutic radiotracer behaves identically to the diagnostic
radiotracer in vivo, which is crucial for accurate dosimetry.
•This is in contrast to nonchemically identical matched pairs (e.g.,
111
In/
90
Y),
where diagnostic information is less representative of therapeutic dose
distribution due to differences in radiotracer behavior.
32

33. Ideal Radiopharmaceutical
•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 as follow:
33

34. 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 radiopharmaceuticals.
•The geographic distance between the user and the supplier also limits the
availability of short-lived radiopharmaceuticals.
34

35. 2. Short Effective Half-Life
•A radionuclide decays with a definite half-life, which is called the physical half-life,
denoted Tp (or t
1/2). The physical half-life is independent of any physicochemical
condition and is a characteristic for a given radionuclide.
•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 (T
b). It
is the time needed for half of the radiopharmaceutical to disappear from the biologic
system and therefore is related to a decay constant,
•λ
b=0.693/T
b
35

36. •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.
•The net or effective rate λe of the loss of radioactivity is then related to the physical
decay constant λp and the biologic decay constant λb. Mathematically, this is
expressed as
36

37. •The effective half-life T
eis always less than or almost equal to the
shorter of T
por T
b.
•For a very long T
pand a short T
b, T
eis almost equal to T
b.
•Similarly, for a very long T
band a short T
p, T
eis almost equal to
T
p
•Radiopharmaceuticals should have a relatively short effective half-
life, which should not be longer than the time necessary to
complete the study in question.
37

38. 38

39. •The time to start the imaging of the tracer varies with different
studies depending on the invivo pharmacokinetics of the tracer. The
faster the accumulation of the tracer in the organ of interest, the
sooner imaging should start.
•However, the duration of imaging depends primarily on the amount
of activity administered, the fraction thereof accumulated in the
target organ, and the window setting of the gamma camera.
39

40. 3. Radionuclide Decay
•Radionuclides decaying by α-or β-particle emission should not be used as the label
in diagnostic radiopharmaceuticals, because they cause more radiation damage to
the tissue than do γ-rays.
•Although γ-ray emission is preferable, many β-emitting radionuclides, such as
131
I-
iodinated compounds, are often used for clinical studies.
•However, α-emitters should never be used for invivo diagnostic studies because
they give a high radiation dose to the patient.
•But α-and β-emitters are useful for therapy, because of the effective radiation
damage to abnormal cells.
•No particle emission for diagnostic studies.
40

41. 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.
41

42. •Whatever the mode of decay, for diagnostic studies, the radionuclide must
emit a γ-radiation with an energy preferably between 30keV and 300keV.
•Below 30keV, γ-rays are absorbed by tissue and are not detected by the
NaI(Tl) detector.
•Above 300keV, effective collimation of γ-rays cannot be achieved with
commonly available collimators and can penetrate through the collimator
septa and interact in the detector. This degrades the spatial resolution.
•However, manufacturers have made collimators for 511-keV photons, which have
been used for planar or SPECT imaging using
18
F-FDG.
•γ-Rays should be monochromatic and have an energy of approximately
150keV, which is most suitable for present-day commonly used collimators.
•Moreover, the photon abundance should be high so that imaging time can be
minimized.
•Depending on the invivo pharmacokinetics of the tracer. The faster the
accumulation of the tracer in the organ of interest, the sooner imaging should start.
42

43. 43

44. 5. High Target-to-Nontarget Activity Ratio
•For a 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.
•For a therapeutic study, poor localization might result in an off-target toxicity.
•Therefore, the target-to-nontarget activity ratio should be high.
44

45. •An ideal radiopharmaceutical should have all the above characteristics to provide
maximum efficacy in the diagnosis of diseases and a minimum radiation dose to the
patient.
•However, it is difficult for a given radiopharmaceutical to meet all these criteria,
and the one of choice is the best of many compromises.
45

46. Sterile, pyrogen-free, safe for human use, and is efficacious for a specific indication
FDA approved for clinical usage.
Minimalradiation doseto patient and nuclear medicine personnel
High target to non target ratio
Inexpensive, readily available
Simplepreparation and quality control
Diagnostic
1. Puregamma emitter, no internal
conversion.
2. 30 <gamma energy< 300 kev.
3.Short effective half-life.
Therapeutic
1. Particle emission.
2. Medium/highenergy(>1 Mev).
3.Moderately long effective half-life. Ex: days
46

47. Properties of all injectable pharmaceuticals
•1.Must be sterile and pyrogen-free.
•2.Should be isotonic and have physiological pH
47

48. Radiopharmaceutical
Composition
•Itcanbeastandaloneradionuclidearadioactive
element.
•suchas
133
Xe.
•Xenon-133isaninhaledradiopharmaceuticalimaging
agentprimarilyusedtoimagethelungsandevaluate
pulmonaryfunction.
48

49. Radiopharmaceutical
Composition
•In general, a it consists out of three components:
•Vector
•Radionuclide
•Linker
Radionuclide
•suchas
131
I-iodinated
proteinsand
99mTc
-
labeledcompounds.
49

50. •Aradioactivenuclidebeingresponsibleforasignaldetectableoutsideofthe
organismforsubsequentvisualizationwithnuclearmedicalmethodsortherapeutic
dose.
•Amolecularstructure(biologicalvector)determiningthefateofthe
radiopharmaceuticalwithintheorganism(pharmacokineticsand
pharmacodynamics),determinesthephysiologicalbehaviorofthecompound.
•Theorganicmoleculeactasacarrieroftheradioisotopetospecificorgans,
tissues,orcells.
•Thelinkerformsastablechemicalconnectionbetweentheradionuclideandthe
vectormolecule.
50

51. •For meta radionuclides, a bifunctional chelator is required as linker, which is
a chelator with a reactive functional group.
•This bifunctional chelator forms a stable complex with the radiometal.
•A perfect “radiometal-chelator” pair should aim to form a kinetically inert and
thermodynamically stable complex.
51

52. •Two main classes of chelators have been developed:
macro-cyclics and acyclic chelators.
•Macrocycles, defined as cyclic molecules containing
several donor atoms, present a rigid and preorganized
framework and yet have the conformational flexibility to
wrap or grasp the radiometal with their macrocyclic
structure, making them more thermodynamically stable and
inert to dissociation than their open-chain acyclic
analogues.
•However, macrocyclic chelators frequently present high
kinetic barriers, requiring high temperatures and long
incubation times for optimal radiolabeling, which can
pose a limitation for temperature-sensitive biomolecules
(e.g., antibodies).
•Conversely, acyclic ligands generally present rapid
radiolabeling kinetics due to a less restricted bond rotation
in their free form, which permits the incorporation of
radiometals at room temperature within minutes.
•However, acyclic ligands are not as kinetically stable as
macrocyclic chelators, potentially showing demetallation
and transmetallation reactions in biological systems.
52

53. 53

54. 54

55. 55

56. Vector
56

57. 57

58. •Thevectorisanessentialpartoftheradiopharmaceuticalasitisresponsibleforthe
selectiveinteractionwiththetargettissueleadingtoahigherconcentrationofthe
radionuclideinthetargettissue.
•Thisprovidestheimagecontrastfordiagnosticimagingandselectiveirradiation
ofthetargetcellsfortherapeuticradiopharmaceuticals.
•Vectorsprovidetheradiopharmaceuticalwithhighaffinityandspecificity.
•Thisideallyshouldresultintheefficientdeliveryofradiationtothetargetedtumor,
reducingoff-targetcytotoxicitytohealthytissue.
•Mostvectorshaveasaturablepharmacologic,immunologic,ormetabolic
interactionwiththeirtarget.
•Inthiscaseitisimportantthatonlytraceramountsoftheradiopharmaceuticalare
administeredinordertoavoidsaturationofthetargetandpotential(side)effects
(i.e.donotinduceanyphysiologicalresponseorpharmacologiceffectin
patients).
Vector
58

59. •Typically, these targeting vectors could be:
•small molecules, peptides, ligands and monoclonal antibodies.
•More recently, nanoparticles, including polymers, dendrimers and
liposomes, have been studied.
•The suitability of these vectors and, ultimately, their successful translation
into the clinic depends not only on their affinity and specificity for the target
but also on their stability and pharmacokinetic profile.
•The vector itself often plays a major role in determining the in vivo
biodistribution and specificity of uptake of the radionuclide in malignant tissue
and so, too, its toxicity.
59

60. •Ultimately, identification and optimization of the targeting vector molecules
represents a quickly evolving field in its own right –one which currently plays a
major role in so-called precision or personalized medicine.
•Targeting different stages and addressing the heterogeneity of disease are
currently the subjects of extensive preclinical and clinical research.
•Patient-by-patient dosimetry, administration schemes and the right
choice/combination of therapeutic agents will guide the future of individualized
oncology.
60

61. •a vector (long)
plasma half-life in
combination with a
radionuclide with a
(short) half-life.
Matching targeting
vectors and
radionuclides
61

62. •The various
radiopharmaceutical
constructs that have
been used to deliver
radiation (vectors) are
illustrated:
a)Radioactive element
b)Small molecule
c)Peptide
d)Antibody
e)Nano-construct
f)Microsphere
62

63. •A wide variety of ‘delivery vehicles’ have also been used, including:
•Small molecules that incorporate the radionuclide.
•Radiolabeled peptides and antibodies make up the majority of agents
investigated clinically.
•Liposomal or nano-construct delivery approaches are being
investigated preclinically.
•Glass and resin microspheres are relatively well established; these are
used in the treatment of hepatocellular carcinoma or hepatic metastases
of colorectal cancerand are administered via the hepatic artery.
63

64. •The differential retention of different constructs in the tumors is
important but difficult to generalize.
•Antibody-mediated delivery is bivalent and generally leads to long retention, but
the long circulating half-life of antibodies leads to greater normal organ,
particularly hematological, toxicity.
•By contrast, small molecules and peptides have the advantage of rapid targeting
and clearance but exhibit typically shorter tumor retention.
64

65. •Theretentioninthetargettissuecanbeduetoareversibleinteraction
suchasaffinity-basedreceptorortransporterbindingandbindingto
misfoldedproteins,governedbyequilibriumassociationand
dissociation.
65

66. Engineered agents can be designed that optimize tumor retention while increasing clearance
kinetics.
•Afterbindingtothetarget,thetracermayhoweverbeinternalized
andretainedinthecell,leadingtopseudo-irreversiblekinetics.
•In all cases, if the agent is internalized and the radionuclide retained
intracellularly, the target retention time will be very long compared
with the clearance kinetics of the agent.
66

67. Small Molecules
•Small molecules (their low molecular weight (<900 Da)) are frequently used as
vectors for intracellular targets.
•Due to their membrane permeability, hence they can penetrate the cells, and the ability to
design molecules for specific biochemical targets within the cytoplasm and nucleus.
•They are ideal vectors for targeting intracellular proteins.
•A variety of small molecules can be used as vector molecule ranging from
biochemicals, amino acids, fatty acids, nucleosides, xenobiotics and chelates
(intrinsic radiopharmaceuticals).
•In contrast to larger molecules, small molecules are also more likely to pass through
the blood brain barrier.
•Hence, they can be used for targeting cancers involving the central nervous system.
•In their simplest form, radionuclides with intrinsic targeting properties can be used
therapeutically.
67

68. 68

69. Peptides and Proteins
•Preparation of lead radiopeptides resulted in what is known as peptide
receptor radionuclide therapy (PRRT).
•Peptides that target specific receptors, expressed on specific cancer entities. Moreover, the
overexpression of many peptide receptors on human tumor cells compared to normal
tissues makes these receptors attractive targets PRRT.
69

70. Peptides and Proteins
•Peptides present highly desirable properties such as low or non-
immunogenicity, good pharmacokinetic profiles with short circulation times
and ease of synthesis using either an automated peptide synthesizer or by
manual synthesis, compared to small molecules.
•In fact, peptide-based radiotracers for imaging and therapy have gained a lot
of attention since becoming one of the preferred targeting systems, as
illustrated by the increasing number of these agents moving forward to
clinical trials in recent years.
70

71. •Due to their low molecular weight (peptides are usually classified as containing
less than 50 amino acid residues), peptides show rapid diffusion into target
tissue.
•Upon binding of the radioligand, the receptor-ligand complex is often
internalized, allowing long retention of radioactivity in tumor cells.
•However, an issue often associated with the use of radiolabeled peptides is their
high uptake and retention by the kidneys, which is a concern, particularly for
radionuclide therapy because of potential radionephrotoxicity.
71

72. •Nevertheless, peptides and small molecules face limitations related to their
short in vivo half-lives and low proteolytic stability, which reduce their final
efficacy.
•Current efforts to improve:
•Resistance to proteolysis include cyclization approaches, the use of unnatural
amino acids, and combination with protease inhibitors.
•In vivo half-lives include elongation with polyethylene glycol moieties is
one of the most common strategies to extend the circulation time of peptides,
slowing their clearance in vivo.
72

73. •Proteins can also be used as vector molecule for
radiopharmaceuticals.
•An example is the use of radiolabeled human serum albumin
(HSA).
•HSA (HSA, 66.5 kDa) is a heat-sensitive globular protein with a
primary sequence made up of 585 amino acid residues, and is
the most abundant protein in human plasma (3.5-5 g/dL).
•Its high solubility, stability, and plasma half-life of
approximately 16-18 hours makes HSA the ideal vector for PET
blood pool imaging applications.
73

74. Monoclonal Antibodies
•The other leading class of targeting vectors are monoclonal
antibodies (mAbs).
•Intact mAbs are considered good candidates for targeted
therapy as well as diagnostic purposes, because they provide
a versatile platform of probes with outstanding affinity and
specificity toward a myriad of antigens.
•Their large size (150 kDa), which precludes glomerular
filtration, combined with Fc-mediated catabolism escape,
results in a circulation of several days to weeks in blood.
•The industrial production of mAbs against tumor-associated
antigens has revolutionized the therapeutic oncologyfield.
74

75. Particles
•Particles have been used for a long time as vectors for radiopharmaceuticals and
albumin served as a protein that can be denatured resulting in biodegradable
particles with a size distribution that depends on the denaturation conditions.
•Large particles, such as macroaggregated albumin (MAA), 10-100 mm, are
retained in the first capillary bed downstream of the injection site and are
primarily used to quantify lung perfusion but are also applied for lung shunt
estimation in
90
Y-radioembolization therapy.
•MAA particles are usually labeled with
99m
Tc, but labeling with 68Ga or 18F for application in
PET has also been described.
•Smaller particles (99mTc-labeled nanocolloids) are majorly used for surgical
planning of sentinel node resection and combination with a fluorescent tag into
“bimodal particles” allows for optical surgical guidance toward the sentinel node.
75

76. Nanoparticles
•Nanoparticles are the most recent candidates to emerge as vectors.
•Their physicochemical properties (size, surface and shape) are highly
tunable via different core/shell materials and passivating agents, making
them very versatile tools for radiopharmaceuticals.
•These offer the potential for delivery of a very high payload to tumor either
through attachment of radionuclide to their surface or, in the case of hollow
nanoparticles, encapsulation of radionuclide.
•Nanoparticles hold the potential to be functionalized with multiple
radionuclides as well as targeting agents, making them the ideal platform for
holding theranostic pairs.
•Additionally, multiple imaging modalities can be achieved by loading them
with more than one functionality,whereas size and shape directly impact
in vivo biodistribution and pharmacokinetics.
76

77. •Liposomes, about 100 nm in diameter, were the first type of nanoparticle to be
investigated.
•For example, liposomes loaded with
225
Ac and conjugated to trastuzumab were shown to bind and
internalise into HER2/neu overexpressing cells.
•Increasingly sophisticated, multimodality nanoparticles have been engineered.
•For example, folate-targeted poly(lactic-co-glycolic acid) copolymer nanoparticles that encapsulate
docetaxel and are labelled with
90
Y have been designed for combined chemoradiation therapy of
peritoneal metastases in ovarian cancer.
•Other nanoparticle formulations, capable of routing therapeutic radionuclides to tumors,
include dendrimers, carbon nanotubes, and mesoporous silica nanoparticles.
77

78. Cells
•Autologous cells can also be used as a
vector.
•
99m
Tc-red blood cells labeled in vitro or in
vivo are used for ventriculography,
visualization of hemangiomas, and
gastrointestinal bleeding.
•
99m
Tc-labeled autologous leucocytes are
routinely used to image infections.
78

79. 79

80. 80

81. 81

82. •They will undergo radioactive decay due to this instability and result in
emission of either particles and/or electromagnetic radiation and as a
secondary effect X-rays, conversion electrons and Auger electrons, to reach a
more stable configuration.
•Radionuclides occur naturally or are artificially made using cyclotrons,
particle accelerators or are generated by decay of other radionuclides and
obtained from radionuclide generators.
Radionuclide
82

83. •A rapidly expanding number of radionuclides with a broad variety of half-
lives, emission types, and energies makes it possible to carefully pick the
best matching radionuclide for a certain application.
Radionuclide
•Depending on the decay properties of the
radionuclide, it can be used for diagnostic, and/or
therapeutic applications.
•Diagnostic radionuclides emit radiation that
minimally interacts with biological tissue,
allowing it to easily escape the body and reach
external detectors.
•Therapeutic radionuclides emit radiation intended
to maximally interact with surrounding tissue in
order to exert a toxic effect locally.
•These differences in radiation behavior are
heavily reliant on the decay characteristics.
83

84. 84

85. 85

86. Radiopharmaceuticals
metal-based
metal-essential metal-nonessential
Nonmetal-based
(organic derived)
These classes primarily differ in
their strategy of radionuclide
incorporation.
The distinction between these
classes is the role of the
radiometal.
•The radiometal is fundamental
for biological targeting
•Metal-essential drugs are simple
to synthesize, they are
challenging to derivatize.
•Metal-nonessential tracers are
modular by design and in
theory exhibit metal-
independent in vivo behavior.
86

87. •In 2014, of the 47 FDA-approved radiopharmaceuticals:
•16 nonmetallic radionuclides.
•including
11
C,
13
N,
18
F,
123
I,
125
I,
131
I,
133
Xe
•31 metallic radionuclides (radiometals).
•Whose application is becoming prevalent, due to their wider range
of nuclear and physico-chemical properties, rich coordination
chemistry and availability.
87

88. •Organically derived radiopharmaceuticals incorporate:
•Nonmetal radionuclides (e.g.,
18
F,
11
C,
13
N,
15
O, and
123
I) by
covalent bond formation, often replacing one hydrogen atom,
whereas
•Metal-based tracers rely on coordination chemistry.
•The short half-lives and limited decay characteristics of most
“organic” radionuclides severely limit their applications.
•Radiometals offer a broad variety of decay characteristics.
88

89. 89

90. 90

91. 91

92. Assignment 1
92
Name Topic: production of
radionuclides
Delivery date
Soft copy
Presentation date
تاحش
ميهاربا
ىفطصم
-Cyclotron-produced
-Generator-produced
15.10.2025 22.10.2025
دمحم
ىيحيماما
Reactor-produced:
-(n,γ)
-(n,f)
15.10.2025 22.10.2025