A presentation on health care applications of radioisotopes

1. Madhava B Mallia
Radiopharmaceuticals Division
Radiochemistry and Isotope Group
BHABHA ATOMIC RESEARCH CENTRE
Trombay, Mumbai - 400 085, INDIA
Radioisotope Applications In Health
Care

2. Radiation
Radioisotope
Radioactivity
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3. Radioisotopes
HEALTH CARE
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4. “Ocuprosta” seeds for brachy therapy of
occular & prostate cancer
Bhabhatron
(Image guided teletherapy machine)
Radioisotopes
Radiopharmaceuticals
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5. Radiopharmaceuticals
Molecules tagged with a radioisotope used for diagnosis or therapy of various
diseases or to evaluate function of various organs
+
Radioisotope Biomolecule Radiopharmaceutical
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6. RADIOPHARMACEUTICALS
Diagnosis Therapy
Detection of the disease Treatment of the disease
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7. Diagnosis
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8. TRACER
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9. Tracer
Signal
Detector
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10. Radioisotope
(Tracer)
Radiation
(Signal)
Radiation detector
(Detector)
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11. Range - γ > β > α
Diagnosis – Gamma radiations
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12. Paracetamol10/26/2020 12

13. Paracetamol Radioactive Paracetamol
Radiosynthesis
Paracetamol Vs Radioactive Paracetamol
Same structure
Chemically identical
Same pharmacokinetics in vivo
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Gamma imaging
Final image showing
radioactivity
distribution

15. Radioisotopes for diagnosis
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Gamma emitting
radioisotopes
Positron
emitting
radioisotopes
Example: Technetium-99m
99mTc 99Tc
140 keV
Gamma
82Rb
Example: Rubidium-82
82Kr
positron
electron511 keV
Gamma
511 keV
Gamma

16. Imaging modalities: SPECT and PET
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SPECT – Single Photon Emission Computed Tomography
PET – Positron Emission Tomography
PET SPECT
Uses a positron emitting radioisotope Uses a single photon emitting
radioisotope
BGO detectors are used NaI(Tl) detectors are used
Images with high spatial resolution are
obtained (2-4 mm)
Images with low spatial resolution are
obtained (8-10 mm)
High cost Relatively low cost
High sensitivity Relatively low sensitivity
High signal-to-noise ratio Low signal-to-noise ratio

17. Targeted radiopharmaceuticals...
• Size and charge
• Lipophilicity
• Body physiology
• Mimicking biologically active molecules
• Antigen-Antibody interactions
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For functional imaging and disease detection

18. Radiopharmaceutical administration...
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Radiopharmaceuticals
Intravenous injection Oral administration

19. Targeting based on size and charge...
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Myocardial perfusion imaging: Detection of Coronary Artery Diseases (CAD)
Different arteries supply blood to different sections of the heart

20. Block in artery
Region of low blood
supply
Myocardial perfusion imaging  Mapping blood supply to heart muscles
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Myocites (Heart muscle cells) need potassium ions (K+) for their function
Myocites receive K+ ions from blood
A tracer that can mimic K+ can therefore be used for myocardial perfusion imaging

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1.33 Angstroms 1.48 Angstroms 1.4 Angstroms
No isotope
suitable for
imaging
Rubidium-82
Half-life – 1.27 min
PET radioisotope
Thallium-201
Half-life – 73 hours
SPECT radioisotope
Potassium ion mimics
Ionic size

22. Targeting based on lipophilicity...
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Myocites (Heart muscle cells) can absorb lipophilic complexes from blood
A lipophilic tracer can therefore be used for myocardial perfusion imaging
99mTc-MIBI
MIBI – methoxy isobutyl isonitrile
+ +
99mTc-Tetrofosmin

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Typical normal
myocardial perfusion
images
99mTc-MIBI
+ +
99mTc-Tetrofosmin

24. Targeting based on physiology...
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Thyroid
Evaluation of thyroid function
Thyroid facts
• Vital hormone gland
• Produces thyroid hormones, T3 and T4
•Plays major role in growth, metabolism
and development of human body

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Hormone T4 Hormone T3
Hormones T4 and T3 require iodine for biosynthesis by thyroid
Thyroid utilizes iodine from out diet to biosynthesis of T4 and T3
Monitoring iodine uptake can provide functional status of
thyroid

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127I- 123I- 124I- 125I- 131I-
Non radioactive Iodine-123
Half-life – 13.13 h
Gamma
Iodine-124
Half-life – 4.18 days
Positron
Iodine-125
Half-life – 60 days
Low energy gamma
Iodine-131
Half-life – 8 days
Gamma
beta
More common

27. Oral administration of Na 131I
Normal thyroid Abnormal thyroid 1 Abnormal thyroid 2
Thyroid scans
Dose for diagnosis: 50 – 100 Ci
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SPECT imaging of thyroid

28. Sending Iodine elsewhere!! Mimicking Biomolecule for
cellular targeting
Oral administration of Na 131I
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29. Bus to New Delhi
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Pheocromocytoma
Neuroblastoma
Neuroendocrine cancers
Norepinephrine transporter (protein)
Cell membrane
CytoplasmCytoplasm

31. meta-iodobenzyl guanidine
Analogues
Na131/123I
Exchange labeling
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131I- meta-iodobenzyl guanidine
131I- meta-iodobenzyl guanidine Blue arrows show cancer
lesions
Typical image obtained with
131I-meta-iodobenzyl guanidine

32. 18F-Fluorodeoxyglucose (FDG) for diagnostic imaging of
cancers: Mimicking Glucose
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Mutation Formation of tumour

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Formation of tumour
Metastasis

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Energy needed for cellular functions
Energy comes from metabolism of glucose
Fast multiplying cells need more glucose

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Glucose FDG
FDG
2D - scan 3D - scan

36. Somatostatin receptor scintigraphy: Mimicking
Somatostatin
Somatostatin, a peptide hormone regulates endocrine system
Somatostatin binds to somatostatin receptors
Somatostatin receptors are over expressed in neuroendocrine tumors
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Somatostatin receptors
Somatostatin
Normal endocrine
cells
Cancerous cells
overexpressing
somatostatin
receptor

37. Radiopharmaceuticals with metallic radioisotope
(coordination compounds or complexes)
131I, 18F…etc
Monovalent
Covalent bond
99mTc, 177Lu, 90Y….etc
Multivalent
Coordinate bonds
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38. 99mTc, 177Lu, 90Y….etc
X
Bifunctional chelator approach
Bifunctional chelating agent (BFCA)
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39. Chelator ChelatorFunctional group Functional group
p-amino benzyl DOTA P-NCS benzyl DOTA
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40. Simple organic molecules
Antibodies Peptides
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41. Somatostatin analogue – TOC/TATE
(TOC - Tyrosine-3-Octreotide)
TOC TOC
TATE TATE
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42. Somatostatin receptor
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43. Neuroendocrine Tumors over express somatostatin receptor (SSTR)
Somatostatin receptor
Cancer cells
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44. TOC
Do not disturb!!
DOTA TOC
DOTA
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45. 68GaCl3
DOTA-TOC 68Ga-DOTA-TOC
68Ga- Available from 68Ge/68Ga generator
Eγ - 511 KeV
Eβ
+ - 1.9 MeV
t1/2 - 67.7 minutes
Typical adult patient dose – 2 to 3 mCi
DOTA - 1,4,7,10-tetraazacyclododecane-1,4,7,10-
tetraacetic acid
pH 4.5
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46. HYNIC-TOC
Do not disturb!!
NHS-ester of Hydrazino nicotinic acid (HYNIC)
TOC
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47. 99mTc-HYNIC-TOCHYNIC-TOC
Na99mTcO4, EDDA, Tricine
SnCl2.2H2O
100oC, 20 min
99mTc – Available from 99Mo/99mTc generator
Eγ - 140 KeV
t1/2 - 6.01 hours
Typical adult patient dose – 10 - 15 mCi
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48. Radiopharmaceuticals
99mTc-HYNIC-TOC Blue arrows show cancer lesions
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49. Therapy – treatment of disease
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51. Diagnosis
Therapy
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52. Na131I Therapy for thyroid cancer
Diagnostic dose: 50 – 100 Ci
Therapeutic dose: 50 – 80 mCi
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53. Therapy with 131I-mIBG
Potential sites for pheocromocytoma and neuroblastoma
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54. Norepinephrine transporter (protein)
Cell membrane
CytoplasmCytoplasm
Diagnostic dose: 0.5 mCi
Therapeutic dose: 100 – 200 mCi
Radiopharmaceuticals
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55. Peptide Receptor Radionuclidic therapy (PRRT)
99mTc-HYNIC-TOC68Ga-DOTA-TOC
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56. 177LuCl3, 90YCl3
177Lu-DOTA-TATE, 177Lu-DOTA-TOC, 90Y-DOTA-TATE, 90Y-DOTA-TOC
DOTA-TOC DOTA-TATE
177Lu-DOTA-TATE
177Lu – reactor produced isotope
Eγ - 113 KeV, 210 KeV
Eβ
- - 490 KeV
t1/2 - 6.7 days
Typical adult patient dose – 100 to 200 mCi10/26/2020 56

57. Radiopharmaceuticals
177Lu-DOTA-TATE
Therapeutic dose: 100 – 200 mCi
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58. 99mTc-HYNIC TOC images
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59. Teletherapy
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60. Teletherapy
Use of External beam of radiation for treatment of tumors
• Most widely applied form of radiotherapy
• >60% cancer patients require radiotherapy
• Source – Cobalt-60 (t1/2 ~5 yrs, Eγ >1MeV)
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61. Bhabhatron BARC developed unit supplied in India and abroad (Vietnam, Sri Lanka)
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62. Brachytherapy
“Short Distance” Therapy achieved by implantation of small sealed
radioactive needles, tubes, seeds, wires for specific duration in close
proximity to the tumors.
Sealed capsules
Encapsulated with Iodine-125
Encapsulated with Cesium-137
Encapsulated with Palladium-103
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63. Iodine-125 -Titanium capsule
125I – reactor produced isotope
Eγ - 35 keV
Auger electrons, X-rays
t1/2 - 60 days
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64. THANK YOU....
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