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Efforts of DAE Units have ensured availability of state-of-the-art radiopharmaceuticals at an affordable price to thousands of patients in India everyday: DAE Secretary

The Department of Atomic Energy (DAE), in collaboration with PIB Mumbai, organized a half-day event today to provide an opportunity for the media interested in the sector to get a deeper understanding of issues germane to the field. The theme chosen for the Media Meet was “Radioisotopes in Healthcare – Radiopharmaceuticals for Nuclear Medicine: DAE Roles and Contributions”.

Addressing the gathering, Secretary, DAE and Chairman, Atomic Energy Commission, Shri K. N. Vyas said, “Thanks to the very early, visionary beginning given to Indian atomic energy programme by Dr. Homi J. Bhabha, Apsara reactor was built in 1956 and put to wide use, including for production and applications of radioisotopes. Among the myriad uses of radioisotopes, use of radio(active)pharmaceuticals – formulations or radioisotope labelled compounds – has emerged as a major field in medicine, namely, Nuclear Medicine (NM). DAE has remained in the forefront of R&D and production of a variety of radiopharmaceuticals for supply to hospitals and nuclear medicine centres across the country. The sustained, collective efforts of DAE Units have ensured the availability of the state-of-the-art radiopharmaceuticals in India at an affordable price, thus serving thousands of patients every day. The DAE programme on ‘radiopharmaceuticals for nuclear medicine’ is thus a true testament to its motto, ‘Atoms in the Service of the Nation’.”

Former Chairman, BRIT and Chief Executive, BRIT and Associate Director, Isotope Group, BARC, Dr. N. Ramamoorthy said, “DAE has taken sustained efforts towards ensuring indigenous availability of established radiopharmaceuticals as well as to develop emerging ones for state-of-the-art NM services in India. Many such products are being regularly used for serving patients and some others are undergoing clinical evaluation. This has not only ensured the availability of many of the recently emerging radiopharmaceuticals, but has also made them indigenously available at an affordable cost to the patients in our country.”

Four presentations were made on the occasion, by scientists and practising doctors, led by Dr. P. K. Pujari, Associate Director, Radiochemistry & Isotope Group, DAE.

Highlights of the presentations are given below.

Radiopharmaceuticals and Allied Radioisotopes: Part I

In his presentation on the above topic, Dr. Tapas Das, Radiopharmaceuticals Division, Bhabha Atomic Research Centre elucidated the basic concepts of radiopharmaceuticals and provided a brief overview of various radioisotope-based formulations available from DAE for the service of mankind.

‘Radiopharmaceuticals’ are a special class of formulations of radioisotopes, suitable for administration to patients for diagnosis or therapy of several specific ailments.

Diagnostic Radiopharmaceuticals are designed to provide images of intended specific organ or disease cites (lesions). Present day nuclear medicine physicians are equipped with more than one hundred Nuclear Medicine imaging procedures covering virtually every major organ system of the human body.

Therapeutic applications of radiopharmaceuticals are based on the well-known principle that the ionizing radiations, especially the particulate emissions, have the ability to destroy cells by depositing their energy. The use of Therapeutic Radiopharmaceuticals is rapidly gaining momentum beyond treatment of thyroid disorders and is playing important roles, particularly in cancer.

Development of any new radiopharmaceutical is a significant challenge and requires the combined expertise of different branches of science, such as chemistry, biology, physiology, veterinary science and medicine.

Department of Atomic Energy (DAE) has been rendering support to robust R&D as well as delivery of products of medically important radioisotopes. Several important radioisotopes such as, Molybdenum-99, Iodine-125, Iodine-131, Samarium-153, Lutetium-177 are produced regularly using Dhruva reactor and Fluorine-18 using the medical cyclotron facility and supplied to the hospitals all over the country through the Board of Radiation and Isotope Technology (BRIT).

DAE produces a wide variety of radiopharmaceuticals and freeze-dried kits and supplies them on regular basis to the hospitals across the country. The efforts undertaken by the DAE scientists in the recent time have helped in developing several state-of-the-art radiopharmaceuticals; some of which are being regularly used for imaging and treatment of patients. Indigenous preparation of these radioactive agents or freeze-dried kits not only ensures the availability of most modern radiopharmaceuticals to the Indian population, but also their affordability to the major cross-section of Indian patients.

Radiopharmaceuticals and Allied Radioisotopes: Part –II

Dr. Anupam Mathur, Board of Radiation and Isotope Technology (BRIT) described the major services related to supply of radiopharmaceuticals and medical radioisotopes handled by the BRIT, a unit of DAE. Regular production and supply of the most widely used products are made by BRIT in close coordination with BARC, availing the radioisotopes produced in Dhruva reactor. The presentation provided a pictorial representation of the cycle of production of radiopharmaceuticals starting from reactor to patient use. It listed the major radiopharmaceuticals, both for diagnostic imaging (PET and SPECT) and therapy, supplied on regular basis for patient use in nearly 300 nuclear medicine centres and highlighted the frequency and quantum of their production.

A few of the noteworthy contributions include kits for the production of organ or disease-specific 99mTc radiopharmaceuticals (for SPECT imaging) and 131I-based products (for both therapy and diagnosis). Nearly 70-80% of the requirements of the Indian nuclear medicine centres with respect to the above two groups of products are being met by current supplies by DAE. BRIT and RMC of BARC jointly operate the medical cyclotron facility at Parel and supply the important product called Fluorine-18-FDG and some other products for PET imaging, to users in and near Mumbai. Lutetium-177 based therapy products, recently developed at BARC are also being scaled up and supplied from BRIT, mainly for management of cancer patients. The presentation also touched upon some of the upcoming facilities of DAE for introducing new radiopharmaceuticals as well as for enhancing and/or strengthening the production capacity of some of the existing products, for example Mo-99/Tc-99m generators.

Applications of Radiopharmaceuticals for Nuclear Medicine Services: Part – I

Dr. Sandip Basu, Consultant Physician and Head, Nuclear Medicine Academic Programme, Radiation Medicine Centre, BARC informed that two major Clinical Nuclear Medicine Centres under DAE serves patients in this country: (a) Radiation Medicine Centre (RMC), a Division of BARC instituted by Dr. Homi Jehangir Bhabha in the year 1963 and housed at Tata Memorial Hospital Annexe Building at Parel, Mumbai; and (b) Department of Nuclear Medicine of Tata Memorial Hospital, a DAE-aided Institute, housed at Tata Memorial Hospital Main Building at Parel, Mumbai.

At the level of Clinical departments, the primary mission constitutes (a) Patient Services: through use of radioisotopes in diagnostic and therapeutic procedures of Nuclear Medicine; (b) Basic Clinical Research (Bench to Bedside): Clinical translation of new radiopharmaceuticals to patients; (c) Human Resource Development: Trained manpower development through Education (Post Graduate Doctors and Technologists).

Major Nuclear Medicine Therapies undertaken: (a) 131I (Radioiodine) for thyroid cancer; (b) 177Lu-DOTATATE for metastatic/ advanced Neuroendocrine Tumor; (c) 177Lu-PSMA treatment for Metastatic Prostate Cancer.

DAE’s indigenous radiopharmaceutical programme has provided a major boost not only to the functioning of these two centers, but also to the entire NM therapeutic services offered by other centres in the country.

Both these departments also run an impressive HRD program which offer postgraduate degree viz. MD in Nuclear Medicine to medical doctors as well as DMRIT/DFIT (Diploma in Medical Radio-Isotope Techniques / Fusion Imaging Technology) to Nuclear Medicine Technologists for working in Nuclear Medicine Centres. The training programmes at RMC started way back in 1973: today, nearly 70% of the Nuclear Medicine Physicians at different centres and the Professors and HODs of major Institutes like AIIMS, PGI, JIPMER, CMC Vellore have received their formal training in this Institute.

The multiple mandate of Department of Atomic Energy includes providing cancer treatment at affordable cost has been made a reality by improved Nuclear Medicine procedures developed in the two Institutes, RMC and TMC.

Applications of Radiopharmaceuticals for Nuclear Medicine Services: Part – II

Dr. Venkatesh Rangarajan, Department of Nuclear Medicine & Molecular Imaging, Tata Memorial Hospital, Tata Memorial Centre threw light on the use of nuclear medicine in the evaluation of myocardial perfusion, which visualises microcirculation in heart and gives an entirely different information critical to the decision making process for selecting appropriate treatment. The information provided is complementary to the information provided by angiography. The cardiac viability study done with the help of PET & SPECT scan provides crucial information on the improvement of function after a cardiac treatment. More than 60,000 studies are conducted in a year across the country.

Paediatric nuclear medicine is the subspecialty in nuclear medicine where isotopes are used in diagnosis and treatment of diseases of children. This is more than 50 years old. The small amount of dose being injected and children-friendly studies, make these studies popular among paediatric physicians and surgeons. It provides critical information on the kidneys and other organs to the treating doctor. More than 36,000 studies are done in a year.

Hybrid imaging, especially PET/CT, has made a revolution in oncology. The scan involves collecting a computerized tomography series and a Positron emission tomography series. Seeing both the series and the fusion imaging reveals the disease accurately. The better accuracy has resulted in correct staging, detection of early recurrence, treatment response evaluation and end treatment evaluation. The 18 F FDG PET/CT is useful in almost all cancers. The 18F Fluoride images skeleton better, 18 F FLT detects cell growth accurately, 18 F FMIZO identifies hypoxia and FET detects brain tumours accurately.

The hybrid PET/CT has made such a tremendous impact on cancer treatment that the number of PET/CT centres has increased from one in 2004 to 225 now. The Tata Hospital itself performs more than 20,000 scans in a year.

Director General (West Zone), Ministry of Information & Broadcasting, Government of India, Shri R. N. Mishra was also present on the occasion. Shri Mishra applauded the respectable contribution which the DAE has been rendering to the nation through the years; he appreciated the Department for organizing this media outreach initiative, which he hoped would lead to more informed, in-depth and insightful reporting by the media, on issues concerning this important sector, leading to a greater citizen understanding, appreciation and engagement with the programmes and decisions of the Department.

Additional Background Information

• Radiopharmaceuticals Division of BARC and the Board of Radiation and Isotope Technology (BRIT)have been instrumental in catering to the radioisotope requirement of the country for medical users, as well as for industrial and other applications. Using the Dhruva reactor at BARC, products are made and supplied to various hospitals and nuclear medicine centres. An additional production facility for Iodine-131 is currently being set up in BARC to enhance production capacity for this important radioisotope.
• Radiopharmaceuticals Division of BARC is primarily engaged in indigenous development of effective and affordable diagnostic and therapeutic products as well as kits for their preparation. Some important products developed in the recent years are for management of cancer patients, by PET and SPECT imaging, of neuroendocrine cancer and of prostate cancer. Some products have also been developed fortargeted therapy of liver cancer, treatment of non-Hodgkin’s lymphoma, as well as for bone pain palliation. Most of the technology and know-how are transferred to BRIT for regular production and supply to NM centres for serving patients.
• BRIT supplies radiopharmaceutical products to around 250 NM centres of the country. The NM centres are located not only in large metro cities but also in 2^nd tier cities across our country, pan-India presence. Major products in regular supply are: I-131 products over 500 Ci per annum (Sodium iodide I-131 solution and capsules; I-131-MIBG injection; I-131-Lipiodol); Mo-99/Tc-99m generators [~35 generators per week of 300 mCi, 500 mCi, and 1 Ci capacity]; kits for Tc-99m compounds [19 types; over 1000 kits per month]; Sm-153-EDTMP; Lu-177-EDTMP; Lu-177-DOTA-TATE. Recently BRIT has launched (since Sep. 2018) supply ready-to-use ⁶⁸Ga-labeled diagnostic radiopharmaceuticals (⁶⁸Ga-PSMA-11; ⁶⁸Ga-DOTA-TATE); 50 doses of these products have been supplied to 6 NM centres located in and around Mumbai. This is proposed to be progressively expanded in future depending on NM Centres’ response.
• Radiation Medicine Centre (RMC) of BARC (started under AEET in 1963) has a large-volume NM programme, covering diagnostic and therapeutic services, training & education (HRD) and research. Radioiodine therapy is given for thyroid cancer and hyper-thyroid patients and RMC has the largest registry of thyroid cancer patients in India. From 2015 onwards, on an average, annually ~800 patients receive radioiodine therapy and ~700 patients for neuroendocrine cancer. A notable recent achievement for prostate cancer management usinganother theranostic pair, in-house formulated ⁶⁸Ga-PSMA for PET imaging and ¹⁷⁷Lu-PSMA for therapy leading to metastatic diagnosis in 300 prostate cancer patients and treatment of 150 patients.
• The country’s first medical cyclotron facility set up in 2002 at RMC basement, along with the associated radiopharmacy lab, synthesis modules etc., and operated jointly by RMC-BARC and BRIT, is engaged in producing Fluorine-18-based PET radiopharmaceuticals (6-day/week operation). The major product is ¹⁸F-Fluoro-deoxy-glucose, [¹⁸F-FDG], produced twice a day and used (mostly for PET imaging of cancer) at RMC and Tata Memorial Hospital (major user), as well as supplied to 10 other hospitals in Mumbai. This is the only facility in western India producing ¹⁸F-Sodium fluoride, used in PET imaging of metastatic bone cancer.
• RMC has been running an important HRD programme since 1970s, which offers postgraduate diploma/degree, viz. DRM, DNB, MD in Nuclear Medicine to doctors, and DMRIT (PG Diploma in Medical Radio-Isotope Techniques) to technologists. Nearly 70% of the NM centres in India are manned by staff who have received their education and training at RMC-BARC.
• Tata Memorial Centre (TMC), a grant-in-aid institution under DAE, is one of the leading centres for the prevention, treatment, education and research in cancer. The Tata Memorial Hospital (TMH) of TMC provides NM services and also conducts MD Nuclear Medicine and Post-graduate Diploma in fusion imaging techniques. In addition, TMH has recently started a programme, in collaboration with the Radiopharmaceuticals Division of BARC, to use radiolabelled monoclonal antibodies as therapeutic option for cancer patients. This approach seeks to combine the intrinsic strength of the immune mechanism of the antibody, synergised with radiation from the therapeutic radioisotope, to more effectively destroy the cancer cells. This modality is expected to bring down the cost of treatment with antibodies alone (currently lakhs of rupees per patient) to one-fourth or less. Products under evaluation are for treatment of CD20 positive lymphomas; for treatment of HER2 positive breast cancers.
• Most of the precursor chemicals, biomolecules and linker compounds required for radiopharmaceuticals are not easy to import and quite expensive too. Thanks to multi-disciplinary competencies available at BARC, in-house synthesis is underway for many such precursor products (peptides, linker molecules) to bring down the cost of the final products.