Radionuclides Radiation Tools for Betterment of Humankind Meera

Radionuclides & Radiation : Tools for Betterment of Humankind Meera Venkatesh Radiopharmaceuticals Division Bhabha Atomic Research Centre

15 th July 06

Radionuclides – What are they? l l Unstable nuclides of elements Emission of energetic rays in the process of becoming a different, more stable nuclide l 15 th July 06 Radioactive rays

Radionuclides - Properties l Emission of Radiation l l alpha ( ), beta ( ) : particulates gamma ( ) : non-particulate energetic; varying energies Transient - non-permanent l concept of half life; varying half-lives 15 th July 06

Radiations : , , l l l 15 th July 06 energetic interact with matter to deposit the energy the radiations are easily measurable at very low amounts - high sensitivity the material may alter and its properties may change – e. g. polymerisation the radiation will attenuate after interacting with the material – e. g. its energy reduces, intensity reduces

Some Areas of Impact l Medical l l Agriculture l l radiography, tracers, gauging, radiation processing Research l 15 th July 06 food preservation, tracers, mutation Industry & Hydrology l l diagnostic, therapeutic, sterilization tracers. . .

Radioisotope/Radiation Applications : Basis l l l Easy detectability : Tracers Alterations in the material on irradiation Attenuation in the radiation itself 15 th July 06

Easy detectability of radiation l Tracer applications - Medical l Diagnostic in-vivo Nuclear Medicine; l l l Diagnostic in-vitro radiometric kits l 15 th July 06 static imaging of organs; dynamic imaging of organs; understanding the functioning of vital organs; delineation of tumours etc. hormones/drugs/antigens measurement in biological samples

l Tracer applications - industries, water management l l Tracer applications - laboratory & agricultural tracers; l 15 th July 06 trouble shooting; hydrology applications; process development/optimisation, monitoring industrial reactions etc. process understanding; optimisation of manure/ pesticide; fate of the used manure/pesticide etc.

Radioisotope/Radiation Applications : Basis l l l Easy detectability : Tracers Alterations in the material on irradiation Attenuation in the radiation itself 15 th July 06

Alterations in the material l l 15 th July 06 damage to living cells, death of living organisms - fungi, bacteria, cancer cell. . polymerisation of monomers creation of defects in materials - crystal structure breaking of very tough materials

Damage to living cells l l Fungi, bacteria. . ; food preservation by irradiation; sterilization of medical products by gamma irradiation; blood irradiation cancer cells ; teletherapy, brachytherapy, invivo therapy - radiopharmaceuticals, locoregional therapy 15 th July 06

l polymerisation of monomers; l l breaking of very tough materials l l radiation processing of wires, cables, ‘O’ rings etc. degradation of polymers, teflon etc. creation of defects in crystal structure l 15 th July 06 colouration of diamonds

Radioisotope/Radiation Applications : Basis l l l Easy detectability : Tracers Alterations in the material on irradiation Attenuation in the radiation itself 15 th July 06

Attenuation in the radiation l intensity decrease l information about the material - uniformity, thickness, defects etc. l Gamma radiography ; status of/defects in materials Nucleonic gauges; thickness, level measurements l 15 th July 06

Which radionuclides or radiations? Selection Criteria l Emission properties l type of radiation, energy Half life l Chemistry l Feasibility l Cost l 15 th July 06

Medical use of Radiation & Radioisotopes Diagnostic Therapeutic In-vivo Radiopharmaceuticals Brachytherapy In-vitro radiometric assays Radiation processing Teletherapy Gamma knife Sterilization, Blood Irradiation Polymerized products : hydrogel, drug delivery systems 15 th July 06

Radiopharmaceuticals l Molecules containing Radioactivity used in Medicine - for Diagnosis & Therapy Diagnostic Products In-vivo injectibles oral In-vitro Radiometric assays 15 th July 06 Therapeutic Products In-vivo injectibles oral Sealed Sources Brachy Therapy Topical Applications

Diagnostic Radiopharmaceuticals l l In-Vitro : ‘in-glass’ or outside the body Radiometric Assays (RIAs & IRMAs) l l l Nobel prize winning technology (Dr Yalow-1976) Very useful tool in diagnosing diseases related to hormones; indispensable in pathology labs More recently use in various areas : Tumor Specific Antigens, viral antigens, drugs with narrow therapeutic index, non-clinical applications l l 15 th July 06 IRMA- Prostate Specific Antigen - Prostate Cancer RIA-Aflatoxin B 1 - mycotoxin - food commodities

Radiometric Assays l l l Analytical techniques to measure minute quantities of an analyte in a complex matrix Use of radiolabeled molecule as the tracer Utility in Medicine, Environment, Food industry etc. 15 th July 06

Concentration Substance 10 mmol/L 1 Glucose 100 10 umol/L 1 15 th July 06 Albumin Creatinin Iron Immunoglobulin 100 10 nmol/L 1 Thyroxin, Cortisol 100 10 pmol/L Insulin Free T 3 Progesterone, Testosterone, T 3 Estradiol Endocrinology, Oncology Drug development Pharmacology & toxicology Non clinical fields

Diagnostic Radiopharmaceuticals : in-vivo l l In-Vivo : ‘inside the body’ Static Imaging l l l Organ size, shape, abnormalities etc. Thyroid, Liver, Kidneys, Brain, Skeleton, Lungs, malignancies l Presence of nodules, tumours, metastatic lesions, goitre, abcess, shrinkage etc. Dynamic Imaging l l Functioning of the organ, rate, output, defects etc. Heart, Liver, Kidneys l Infarcted myocardium, hole in the heart, filtration defects in kidneys etc. 15 th July 06

Nuclear Medicine – for imaging Very safe l Non-invasive l No reactions or side effects l minimal radiation dose l 15 th July 06

Uniqueness of a nuclear scan l l l X-ray, USG, CT & MRI – give anatomic information. Nuclear scan provides unique FUNCTIONAL as well as ANATOMIC INFORMATION A highly sensitive technique; also known as Molecular Imaging Available for almost every organ / system 15 th July 06

Example: Functioning of heart muscles Typical heart scan - dynamic showing various regions for easy diagnosis of functioning and quantification of results 15 th July 06

Static images of thyroid with Na 99 m. Tc. O 4 Avid Uptake with increased TSH Iodine Deficiency Goitre Normal Cold Nodule - Rt Lobe Lingual Thyroid Avid Uptake with increased T 3& T 4 Toxicosis 15 th July 06

WHOLE BODY BONE SCAN for skeletal metastases in patients with known or suspected cancer. 99 m. Tc MDP Bone Scan Normal 15 th July 06 Multiple Metastases Ca Prostate Ca Lt Breast

Positron Emission Tomography: PET l l l Recent technology 18 F-Fuloro deoxy glucose (18 F-FDG) most widely used tracer for PET 3 D picture of defects, clear, precise Most often used to find out recurrence of cancers Also used to image heart and brain to find tissues that are not ‘alive’ (do not take up glucose) 15 th July 06

Example : PET machine & PET image 15 th July 06

Therapeutic Radiopharmaceuticals l l l l Deleterious effect of ionising radiations on cells/organisms In-vivo & Sealed Sources Primarily Cancers; others : hyperthyroidism, radiation synoviorthesis etc. Historically very old ; non-systematic Systematic - Old - 131 I, 32 P Surge - past 15 years Forecast : sales 0. 5 B USD now to 2. 8 B in 2007 15 th July 06

Range of particulate radiations 10 d 1 c Range 0. 1 (mm) a : cell nucleus b : single cell c : few cells d : 100 cells b 0. 01 a Auger e- 5. 3 Me. V , 0. 15 Me. V - 1. 7 Me. V 15 th July 06

Therapeutic Radiopharmaceuticals l Palliative - Bone pain l l Liver cancer treatment l l Radiolabeled phosphonates 89 Sr Chloride, 32 P-phosphate, 153 Sm-EDTMP, 188 Rel HEDP , 188 Re-CTMP, 177 Lu-DOTMP, 175 Yb-DOTMP colloids/particulates - through hepatic artery 166 Ho-chitosan, 90 Y-glass microspheres, 188 Re-Sn l colloid Radiation Synoviorthesis l 15 th July 06 colloids/particulates : intra articular injections 166 Ho-Hydroxyapaptite(HA), 153 Sm-HA, BARC l clinical trials and supply

Example: Treatment of rheumatoid arthritis using a radiopharmaceutical 15 th July 06

Brachytherapy l Use of radioactive sources for treatment l l 15 th July 06 Within the tissue Covering the cancer tissue – like amould Within a cavity having cancer Within a vessel to be irradiated

Treatment of Breast Cancer 15 th July 06

Low Energy Radioactive Plaque Therapy for treatment of Ocular melonoma A mushroom-shaped choroidal melanoma Plaque is sewn covering the tumour and removed after stipulated dose delivery (2 -3 weeks) 15 th July 06 Tiny rice-sized {0. 8 mm(OD)x 4. 75 mm(l)} radioactive seeds (15 -25 no. ) are glued into the gold eye-plaque or seed carrier.

Clinical Trials l l Sankara Netralaya, Chennai; 10 Patients successfully treated since Sept. 2003; all doing fine. Product awaiting AERB approval for regular use 15 th July 06

Prostate brachytherapy –within tissues . Prostate cancer is a disease in which cancer cells grow in the prostate. Seed implantation with I-125/Pd-103 seeds (brachytherapy) is a highly effective treatment for men with prostate cancer. Treatment: q Hormone therapy q Surgery q Radiation therapy 15 th July 06

Intracavitary brachytherapy l Encapsulation of small radioactive (137 Cs)tubes(40 m. Ci each). § Location of tumor position. § Implantation of applicator 15 th July 06

External beam radiation therapy Teletherapy § § § 15 th July 06 External source High intensity radiation; 60 Co – most widely used A machine is used to direct the radiation to the tumor (cancer) through the skin.

Indigenous Teletherapy Machine 15 th July 06

Gamma Knife Multiple targeting (up to 201 60 Co sources; 1 TBq each; circular array) to achieve better dose delivery and low damage to surrounding tissues. • Brain tumors • Acoustic neuroma • Arteriovenous malformation (AVM) • Trigeminal neuralgia High accuracy, low risk, low complications, low morbidity 15 th July 06

Radioisotope Applications in Industry Quick, easy, clean and cost saving techniques Sealed Sources l l l Radiation Processing Radiography Testing Gamma Scanning Industrial tomography Nucleonic Control Systems 15 th July 06 Radioactive Tracers l l l Flow rate measurements Inventory Control - chemical plants Leak/blockage detection- pipe lines RTD Studies in chemical reactors Silt movement studies (harbours)

Radiation processing l Gamma rays/ Electron beams l l l 15 th July 06 Medical products sterilization Blood irradiation Polymerisation l Hydrogel l Surface curing of materials-cables, wires, O-rings Processing of sewage sludge Value addition of gems Food & Agriculture industry

Gamma irradiation plant 15 th July 06

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Electron Beam Machine 15 th July 06

Radiation processed Hydrogel for use as Burn/Wound Dressing Product patented Commercialized 15 th July 06

Sewage Sludge Hygienization Facility Vadodara 15 th July 06

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Irradiated Gems – Value addition 15 th July 06

Radiation & Radioisotopes in Food & Agriculture l Radiation Processing l l l l 15 th July 06 Sprout inhibition - potatoes, onions Disinfestation - grains Delayed ripening - bananas etc. Extension of shelf life - strawberries Microbial decontamination – spices, meat Hygeinization – meat, fish Sterilisation – meat, fish, chapatis etc.

FRENCH BEANS UNTREATED 1 k. Gy TREATED 2 k. Gy Shelf-life extension of whole ready –to – cook French beans by radiation processing 15 th July 06 [Storage temperature 100 C] [Storage duration 17 Days ]

POMEGRANATE ARILS UNTREATED 15 th July 06 TREATED 2 k. Gy Shelf-life extension of cut ready –to – eat pomegranate arils by radiation processing [Storage temperature 100 C] [Storage duration 25 Days ]

WHITE PUMPKINS (ASH GOURD) CONTROL IRRADIATED (2 k. Gy) Shelf-life extension of cut ready –to – cook ash gourd by radiation processing STORAGE DURATION 15 th July 06 : 8 DAYS STORAGE TEMPERATURE : 10 0 C

l Mutation l l l Radiotracers l 15 th July 06 High yield -Ground nuts, rice, pulses Disease resistance -mung powdery mildew Enhanced properties -ground nut, jute Early maturity -ground rice, pulses, jute Large seed -ground nut Optimisation of fertiliser use, amounts, time, soil depth etc.

Trombay varieties Released & Notified by Mo. A, GOI for commercial cultivation(2004 -05) Greengram 2005 M: 63 Y: 1100 YI: 20 Eastern UP, Bihar, Jharkhand, Assam and West Bengal 2005 M: 95 Y: 2318 YI: 20 Maharashtra TMB-37 Soybean TAMS-38 Groundnut 2004 M: 120 Y: Summer 2407 YI: 26 2004 M: 110 Y: Kharif 1993 YI: 26 -38 TPG-41 Groundnut TG-37 A Tolerant to yellow mosaic virus Early maturing, resistant to bacterial pustule, Myrothecium leaf spot All India Large seed (65 g 100 seeds) Fresh seed dormancy On farm trials 4551 kg/ha 49% increase Rainy season Rajasthan, Punjab Haryana, Gujarat UP. Rabi/Summer Wider adaptability, seed dormancy W. Bengal. Orissa, Assam/N. E. M=Maturity(days), Y=Yield (Kg/ha), YI= Yield Increase (%) TMB-37 TAMS-38 TG-37 A TPG-41

Trombay Groundnuts in Farmers Field… Receding moisture situation 15 th July 06 Girgaon Karnataka

TROMBAY GROUNDNUT READY FOR THE MARKET 15 th July 06

Radiography l l Easy detection of defects Just like X rays for chest congestion or fractures! 15 th July 06

RADIOGRAPHY TESTING OF AIRCRAFT ENGINE 15 th July 06

FIELD RADIOGRAPHY SYSTEM 15 th July 06

GAMMA SCANNING OF INDUSTRIAL PROCESS COLUMNS 15 th July 06

Tomographic system 15 th July 06

Radiotracer for studying silt movement, dredging etc. in coasts/harbours 15 th July 06

Underground pipeline leakage detection by radiotracer l Long buried pipelines l l l 15 th July 06 Easy detection Exact location Enormous amount of time, labour and money saving

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Detection of underground pipeline leakage 15 th July 06

In Essence …. l l l Radionuclides and Radiation play important roles in many fields that affect human welfare. The impact of nuclear medicine in Medical field is very gratifying In Agriculture and food industry radiation and radioisotope have a significant role to play In industries too the use of radiations is steadily increasing for a variety of purposes The futuristic predictions show an upward trend towards use of radiations/radionuclides 15 th July 06

Acknowledgements l l Dr. Gurcharan Singh, Head, IAD, BARC Dr. S. F. D’Souza, Head, NA & BTD, BARC Dr. A. K. Sharma, Head, FTD, BARC Dr. S. Sabharwal, Head, RTDS, BARC 15 th July 06

Thank You! 15 th July 06