[en] The field of nuclear medicine, which has a long history of more than seven decades, has grown along the path, with several spurts of growth along the way, owing to the availability of new radiopharmaceuticals – new radioisotopes as well as new targeting molecules. For example, the easy and affordable availability of ¹⁸F around the end of last century (although ¹⁸F was one of the radionuclides proposed and studied much long ago) along with the spectacular results of the ¹⁸F labelled glucose; and the research on bio-active/ cellular binding peptides such as somatostatin is followed. The research to develop new radiopharmaceuticals continues with zeal, with the availability of powerful affordable cyclotrons, the unique unequivocal role of nuclear medicine in targeted therapy, availability of a range of therapeutic particle emitting radionuclides (such as radio lanthanides, ⁹⁰Y, alpha emitters etc.) and other factors such as the improved quality of patient management with fusion imaging and accurate dose calculations. Between the lab bench to the bedside of the patient, for every new potential radiopharmaceutical, a series of studies to prove the efficacy and usefulness need to be carried out, which takes a long time; and here, the role of radiation/medical physics is a crucial one. The unambiguous proof that the nuclear medicine procedure using the specific radiopharmaceutical is beneficial to the patient, relies on many factors, among which the dose calculations are very important. In this context, the increasing practice of 'Theranostics' (using a pair of radionuclides either of the same element or of similar chemical properties for diagnosis and therapy, in order to be able to perform accurate dosimetry, which although has been practiced since long ago albeit not under the name of 'theranostics', has received a lot of attention with the availability of a wide range of radionuclides, both for diagnosis, especially for PET imaging and for therapy), is very relevant for the role of radiation/medical physicists. In addition, accurate dosimetric calculations when multiple radionuclides (for example, as a mixture of ¹⁸⁸Re and ¹⁸⁶Re) are administered, would enable larger scope of therapeutic radiopharmaceuticals application. Another area that could benefit from the contributions of dosimetric calculations, is in the new methods of producing well known radionuclides such as ^99mTc (which witnessed a huge shortfall during 2007-2010 periods, and still is a focus of many discussions). The direct production of ^99mTc using cyclotrons has received much attention and the uncertainties regarding the radionuclide impurities and their contributions towards patient dose are still points of concern and debates. Synergistic working of all branches of specialties related to nuclear medicine, lead to new very effective patient care and deserves encouragement. (author)

[en] Prostate Specific Antigen, a serine protease enzyme, of M.W. ∼ 26-33 kDa, is widely considered to be a very useful marker for prostate cancer. It satisfies nearly all the requirements of an ideal 'Tumour Marker' and has hence attracted a lot of attention in the past decade. PSA is present in multiple forms in serum, with an appreciable fraction bound to the protease inhibitor α-1-antichymotrypsin (ACT) and to a small extent to other proteins such as α-2-macroglobulin (AMG) leaving the rest in the free form. The total PSA levels have been reported to have 80% sensitivity and 60% specificity towards the detection of prostate cancer. The lack of specificity occurs mainly due to the high levels of t-PSA in benign prostatic hypertrophy(BPH) apart from the cancer. The concept of free PSA has been introduced in the recent past and the ratio of free/total PSA levels have been shown to be advantageous in the differential diagnosis of BPH from prostate cancer. The f/t ratio is considered to be particularly useful in the grey zones of decision making (t-PSA levels 4-20 ng/mL). The need for the development of assays for total and free PSA is felt due to: a. the high incidence of prostate cancers being detected currently; b. the high cost of tests (higher for free PSA assay, and the cost becomes an important parameter when a patient has to be regularly monitored after therapy) that is not affordable for many patients; c. the potential for research in the area of prostate cancer management where the PSA (total and free) assays will be of great help

[en] Full text: 1. Human seminal plasma collected from many volunteers are pooled and passed through a column of phenyl sepharose equilibrated with 1.25 M ammonium sulphate. Elution is carried out with 1.25 M ammonium sulphate initially, to remove the bulk non-adsorbing proteins. Gradient elution of the absorbed proteins with 0.01 M Tris-HCl, 0.25 M NaCl, pH 7.0 buffer gives a sharp peak containing PSA. At each stage, PSA has to be identified by an independent method such as immunodiffusion or an immunoassay. 2. The absorbed protein peak containing PSA is then lyophilised, redissolved in Tris-HCl buffer and chromatographed in a Superdex-75 or Sephadex-75 column. The absorbed proteins elute out as multiple peaks and PSA is eluted as a sharp peak.At each stage, PSA has to be identified by an independent method such as immunodiffusion or an immunoassay. 3. Step 2 is repeated for better purity. 4. The PSA peak is lyophilised, dissolved in Tris-HCl buffer without NaCl and further purified on an ion exchange column (either anion or cation exchange columns such as DEAE Sephadex or CM-Sephadex or Mono Q). Gradient elution using Tris-HCl buffer without NaCl and Tris-HCl buffer with 0.25 M NaCl resulted in a sharp pure PSA peak (homogenous, sharp single band on SDS-PAGE). This procedure is based on that reported by Wang et al., Oncology, 39,1,1982

[en] Full text: Therapeutic use of radiation and radioisotopes, nearly all of which are artificially produced, is well established. Therapeutic effect in radiopharmaceuticals is due to high LET radiations such as α, β^-, e^- and most therapeutic radiopharmaceuticals employ β^- emitters, produced in nuclear reactors. The list of potential therapeutic radionuclides is large covering few α emitters (e.g. ²¹¹At, ^212/213Bi), mostly β^- emitters (e.g. ³²P, ¹³¹I, ⁹⁰Y, ⁸⁹Sr, ¹⁶⁶Ho, ^186/188Re, ¹⁵³Sm, ¹⁷⁷Lu, ¹⁷⁵Yb, ¹⁶⁹Er), and few Auger/Coster-Kronig/conversion electron emitters (e.g. ^117mSn, ¹²⁵I, ⁷⁷Br). It is reported that in the world there are about 54 research reactors producing radioisotopes, of which 21 have φ<10¹⁴n/s/cm², 26 have φ∼1-5x10¹⁴n/s/cm² and 7 high flux reactors with φ>5x10¹⁴n/s/cm². Although several potential therapeutic radionuclides are identified, unfavourable production logistics narrow the choice, and in some cases high flux reactors become essential. An over-view of the therapeutic radionuclides that can be produced in medium flux nuclear research reactors is attempted. Therapeutic radiopharmaceuticals use radionuclides, mostly for treatment and palliation of cancers and to a lesser extent hyperthyroidism and synovitis apart from explored applicability for prevention of restenosis of blood vessels (endo-vascular radionuclide therapy-EVRT). The need in terms of quantities and specific activities would depend upon the end use. For example, in treatment of liver cancers or synovitis, high specific activity is not essential while to target receptors on cancer cells with radiolabeled peptides, high specific activity preparations are essential. Thus, ⁹⁰Y from ⁸⁹Y(n,γ) ⁹⁰Y can be used in former applications while ⁹⁰Y-lanreotide for treating somatostatin expressing cancers requires ⁹⁰Y from ⁹⁰Sr-⁹⁰Y generator. The production feasibility of an isotope depends on the abundance of the target isotope, neutron absorption cross-section (σ), neutron flux (φ), irradiation duration and co-produced unwanted nuclides and their nuclear characteristics. While intrinsic factors like σ are not amenable to modification, epithermal / resonance absorptions have been used to advantage to attain higher yield and specific activity. We find that yields of ¹⁷⁷Lu and ¹⁵³Sm are always far higher than the calculated yields due to the contribution by the epithermal neutrons. φ and isotopic enrichment of targets are modifiable and play a major role in the choice of the nuclide with production feasibility for therapy. Apart from these, the nuclear reaction itself also plays an important role. Direct neutron capture leads to low specific activity isotope of the target element and high specific activity can be achieved only in reactions with very high ?? and high abundance of the target nuclide. But, reactions resulting in products of an element different from the target, such as (n,p), (n,γ, followed by fission/ β^- /EC decay) could give 'no-carrier added' (NCA) high specific activity products. Some examples from our experience: ¹⁷⁷Lu can be produced by irradiation of natural Lu (¹⁷⁶Lu∼2.6%) by (n,γ) reaction (σ∼2100b) with a specific activity of 5.6-6.7 MBq/μg when irradiated at φ∼3x10¹³n/s/cm² for 7 days. Under the same conditions, 64% enriched ¹⁷⁶Lu (cost ∼ 60 times nat. Lu target) yields 140-180 MBq/μg, which rises to >850 MBq/μg (≥21atom%) on irradiation for 21 days at φ∼9x10¹³n/s/cm², quite suitable for receptor specific radiopharmaceuticals. Though NCA grade ¹⁷⁷Lu can be obtained by the reaction ¹⁷⁶Yb (n,γ)¹⁷⁷Yb(β^-)¹⁷⁷Lu, the quantities are low. Apart from specific activity, absence of chemical impurities is important for radiopharmaceutical applications. Owing to their production routes, the following radionuclides are produced in medium flux reactors in large amounts in h igh specific activities: ³²S(n,p)³²P; ¹³⁰Te(n,γ;β^- decay)¹³¹I; ¹²⁴Xe(n,γ;EC)¹²⁵I; ²³⁵U(n,f)¹³¹I; ⁹⁰Sr; 137Cs. Although enriched ²³⁵U is irradiated specifically for production of nuclides by fission route, long lived nuclides such as ⁹⁰Sr (T_1/228.8y), could be efficiently recovered from the waste from processed irradiated fuel also. The role of epithermal and fast neutrons is significant in production of radionuclides, particularly in threshold reactions. e.g. ³²P yields from one of our reactors (φ_th=1x10¹³ n/s/cm²;2% φ_fast) are more than twice those from another reactor ((φ_th=1x10¹⁴ n/s/cm²;1% φ_fast). Enriched targets enable use of moderate flux reactors for production of adequate quantities of radionuclides. For example, enriched ¹⁸⁵Re and ¹⁸⁷Re could be used for production of ¹⁸⁶Re and ¹⁸⁸Re. For nuclides such as ¹⁷⁵Yb, enriched target would additionally be desired to prevent/minimize concomitant production of unwanted radionuclides. Yb_nat. yields ∼2.2-2.6 MBq/μg ¹⁷⁵Yb with 2.6% ¹⁶⁹Yb+¹⁷⁷Lu, while ¹⁷⁴Yb_99% yields ∼7.4-9.3 MBq/μg ¹⁷⁵Yb of >99.9% RN purity. Several therapeutic radionuclides can thus be produced in medium flux reactors in adequate quantities and of acceptable specific activity. Exploration to identify new therapeutic radionuclides continues owing to the need for varied uses. Few like ^142/143Pr, ¹⁷⁰Tm, ¹⁴¹Ce have potential for therapy and have been explored for production feasibility in medium flux reactors. Additionally, mixed-radionuclide therapy such as in the case of ¹⁸⁶Re and ¹⁸⁸Re (by irradiation of nat. Re target), would merit a fresh look due to the ease of large scale production in many centres and could open more possibilities for production in medium flux reactors. (author)

[en] Radioisotopes and radiation based technologies are widely used in a huge variety of industries to improve efficiency, enhance quality, optimize processes, achieve high performance materials, increase safety, for trouble shooting and so on. Many such applications are not known even to professionals with scientific background. This presentation is aimed at outlining some of these technologies which influence our daily life and contribute to better quality of life. In particular, the role of radiation based techniques in providing better environment through mitigation pollutants in industrial effluents as well as being a clean technology will be highlighted. (author)

No abstract available

[en] ⁹⁰Y and ¹⁰⁵Rh formulations were studied with an aim to prepare therapeutic radiopharmaceuticals. ⁹⁰Y obtained from a ⁹⁰Sr-⁹⁰Y generator as chloride was complexed with known ligands such as DTPA, EDTMP and DOTA as well as a few other phosphonate ligands. Particulates such as ⁹⁰Y labelled ferric hydroxide macroaggregates (FHMA) and ¹⁰⁵Rh-sulphur colloid were prepared and studied for their stability in buffers and human serum. The studies on the complexation of ⁹⁰Y and the preparation of radiolabelled particulates are described. ⁹⁰Y complexed nearly quantitatively with DTPA, DOTA and EDTMP under optimised conditions of reaction pH, temperature and ligand concentrations. Both ⁹⁰Y-FHMA and ¹⁰⁵Rh-S colloid could be prepared in high yields under optimised conditions. The labelled particulates were measuring 20-100 μm and 1-20 μm, respectively and were found to be very stable in buffers as well as human serum at 37 deg. C. The particulates have the potential for use as radiosynovectomy agents and for therapy of cancers such as hepatomas. (author)

[en] Under the coordinated research project (CRP), concerted efforts were made to develop ⁹⁰Sr/⁹⁰Y generator systems to obtain ⁹⁰Y in high yields and of high purity. A two stage ⁹⁰Sr/⁹⁰Y generator based on the supported liquid membrane (SLM) concept was developed in order to obtain ⁹⁰Y in acetate form as well as to minimize ⁹⁰Sr contamination of the ⁹⁰Y product to well below acceptable limits. In 10 h of operation, the generator yielded approximately 85% of highly pure ⁹⁰Y for therapeutic purposes. During the period of the CRP, approximately 1.85 GBq (500 mCi) of ⁹⁰Sr was recovered from high level liquid waste using multistep processes involving, for example, precipitation and ion exchange. A 740 MBq (20 mCi) capacity ⁹⁰Sr/⁹⁰Y generator based on a novel electrochemical procedure was also developed. Since the parent ⁹⁰Sr is a highly radiotoxic isotope, efforts were made to develop quality control procedures to detect ⁹⁰Sr contamination in the ⁹⁰Y eluted from the generator. A novel extraction paper chromatography technique was developed based on the high affinity of the reagent 2-ethylhexyl 2-ethylhexyl phosphonic acid (KSM-17) for ⁹⁰Y. This technique is capable of detecting levels of ⁹⁰Sr as low as 74 kBq (2 μCi) of ⁹⁰Sr in 37 GBq (1 Ci) of ⁹⁰Y. Quality control of the ⁹⁰Y eluted from the SLM based and electrochemical generators showed the ⁹⁰Sr levels to be much less than the allowed limits. (author)

No abstract available

[en] ⁹⁰Y is increasingly accepted world wide as a radionuclide for in-vivo therapy owing to attractive decay features (T1/2 2.67 d; Eβ max 2.28 MeV) and viable production feasibility in high specific activities. ⁹⁰Y is most often recommended for treatment of large tumour lesions as the hard β rays are effective in delivering therapeutic dose to large volume. However, possibility of high radiation dose to the critical organs such as bone marrow and kidneys is an important concern that is given due weightage while designing therapy using ⁹⁰Y. The best route to avail ⁹⁰Y for therapy applications is from ⁹⁰Sr, though neutron actiation of natural ⁸⁹Y(100% abundance) is feasible. The absorption cross section σ is barely 1.38 b, resulting in low specific activity ⁹⁰Y which is useful for limited applications. The possibility of obtaining 90Y through a radionuclide generator as the daughter of a long lived parent ⁹⁰Sr (T1/2 28.9 y) is a major advantage that enables access to high specific activity ⁹⁰Y. Transporting the 90Y activity to a user institution from a centralized production facility is reasonably feasible and this facilitates its wide spread use. Several generator designs have been developed and reported to access ⁹⁰Y. Solvent extraction using a chelating molecule in an organic solvent (0.3M HDEHP/n-dodecane), column chromatography using ion exchange resins (cationic as well as anionic; Dowex-50x8; AG 50x16; Aminex-A5) or inorganic exchanger, membrane based separation using chelating ligand impregnated membranes (CMPO in electrochemical separation are some of the methods reported. Limitations such as elution of ⁹⁰Y after initial elution of ⁹⁰Sr, availability of ⁹⁰Y as a chelated complex which then has to be treated to enable labeling the molecule of interest, possibility of obtaining small quantities of ⁹⁰Y owing to radiolytic damages to the separation system components, paucity of special automation gadgets for handling the high activities remotely, have been some impediments that have delayed the availability of large scale ⁹⁰Sr/⁹⁰Y generators and consequently the wide spread use of ⁹⁰Y. Further, the bone seeking nature of the long lived ⁹⁰Sr+2 has resulted in the very low tolerance limits for ⁹⁰Sr (≤ 74 MBq life time dose), necessitating use of extremely pure ⁹⁰Y. Considering that a patient may require treatment with ∼3.7 GBq ⁹⁰Y several times in life-time, the permissible levels for ⁹⁰Sr is well below 10-4%. Hence, a very clean separation of ⁹⁰Y from ⁹⁰Sr is essential and it is also essential to ensure the quality of the ⁹⁰Y using a reliable, real-time quality control technique. Absence of γ rays in both the nuclides, makes it difficult to quantitate the nuclides, particularly when sub-ppm levels of ⁹⁰Sr has to be measured in ⁹⁰Y. Very few methods have been reported for QC of ⁹⁰Y. Measurement of ⁹⁰Sr levels after decay of ⁹⁰Y, though simple, does not enable QC before clinical use. Use of specific crown ether based resin for retention of trace levels of ⁹⁰Sr enables real-time QC, but is cumbersome and expensive. In this context, the IAEA's CRPs on 'The Development of Therapeutic Radionuclide Generators' and it's sequel 'Development of radiopharmaceuticals based on ¹⁸⁸Re and ⁹⁰Y for radionuclide therapy' have been highly impactive and heartening. Two types of novel generators, namely the 'Supported Liquid Membrane' based generators and the 'Electrochemical Generators' have been developed by us. The latter one, named as 'Kamadhenu', the mythological cow that yields milk eternally, has been developed further as an automated model and ready for deployment. QC of ⁹⁰Y for quantitative estimation of sub- ppb levels of ⁹⁰Sr using a novel simple technique of 'Extraction Paper Chromatography' has also been achieved by us, primarily as a result of the CRP. These important developments have enabled several Member States to start/augment their programs on ⁹⁰Y based radiopharmaceuticals, which is a significant achievement of a CRP, thanks to the IAEA. (author)