Re-utilization of long lived 99Tc radio isotope via Photon induced nuclear reactions.

Technetium-99 is a radioactive waste produced primarily in nuclear reactors. It is also left as radioactive waste in hospitals, directly from 99mTc isomeric state. To bring down the quantity of technetium-99 radioactive waste, the nuclear reactions using photon beam is explored. The integral cross section of the reaction 99Tc(γ,γ')99mTc has been determined using the photo-nuclear activation method. The experiment was done using bremsstrahlung photons having endpoint energies viz. 6, 9, 12, 16, and 20 MeV. 115In(γ,γ')115mIn reaction has been used as a monitor reaction, for the flux normalization of the bremsstrahlung spectrum. Theoretical model calculations have been done using the nuclear reaction code Talys 1.9. Theoretical parameter values are optimized with the presently obtained data. Total cross sections are estimated and investigated the feasibility of re-utilization of the technetium-99 radioactive isotope.

Reactor produced [64Cu]CuCl2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

OBJECTIVE: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade 64Cu via 63Cu(n,γ)64Cu reaction and use it in the form of [64Cu]CuCl2 as a radiopharmaceutical for PET imaging of cancer in human patients. METHODS: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor. The irradiated target was radiochemically processed and detailed quality control analyses were carried out. Sub-acute toxicity studies were carried out with different doses of Cu in Wistar rats. The biological efficacy of the radiopharmaceutical was established in preclinical setting by biodistribution studies in melanoma tumor bearing mice. After getting regulatory approvals, [64Cu]CuCl2 formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients. RESULTS: Large-scale (~ 30 GBq) production of 64Cu could be achieved in a typical batch and it was adequate for formulation of clinical doses for multiple patients. The radiopharmaceutical met all the purity requirements for administration in human subjects. Studies carried out in animal model showed that the toxicity due to "cold" Cu in clinical dose of [64Cu]CuCl2 for PET scans would be negligible. Clinical PET scans showed satisfactory uptake of the radiopharmaceutical in the primary cancer and its metastatic sites. CONCLUSIONS: To the best of our knowledge, this is the first study on use of reactor produced [64Cu]CuCl2 for PET imaging of cancer in human patients. It is envisaged that this route of production of 64Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities.

A simple and robust method for radiochemical separation of no-carrier-added 64Cu produced in a research reactor for radiopharmaceutical preparation.

Copper-64 is an excellent theranostic radiometal that is gaining renewed attention of the clinical community in the recent times. In order to meet the increasing demand of this radiometal, we have demonstrated the viability of its production via 64Zn (n,p) 64Cu reaction in a nuclear reactor. A semi-automated radiochemical separation module based on selective extraction of 64Cu as dithizonate complex was developed. The maximum available activity at the end of irradiation was ~ 700 MBq. The overall yield of 64Cu after the separation process was >85% and it could be obtained with ~12 GBq/µg specific activity, >99.9% radionuclidic purity and >98% radiochemical purity. The separated 64Cu could be utilized for preparation of a wide variety of radiopharmaceuticals.

A facile method for electrochemical separation of 181-186Re from proton irradiated natural tungsten oxide target.

Routine availability of high specific activity 186Re would provide a significant boost to the development of potent theranostic radiopharmaceuticals. In the present study, 181-186Re was produced by proton bombardment (12 MeV, average beam intensity 180 nΑ) for 60 h on natural tungsten oxide target. A facile electrochemical method has been developed for radiochemical separation of Re radioisotopes from irradiated target material. The overall yield of the process was >80% and Re radioisotopes could be separated in a form suitable for preparation of radiopharmaceuticals.

Production of gaseous radiotracers for industrial applications.

This paper describes prerequisite tests, analysis and the procedure for irradiation of gaseous targets and production of gaseous radioisotopes i.e. argon-41 ((41)Ar) and krypton-79 ((79)Kr) in a 100MWTh DHRUVA reactor located at Bhabha Atomic Research Center (BARC), Trombay, Mumbai, India. The produced radioisotopes will be used as radiotracers for tracing gas phase in industrial process systems. Various details and prequalification tests required for irradiation of gaseous targets are discussed. The procedure for regular production of (41)Ar and (79)Kr, and assay of their activity were standardized. Theoretically estimated and experimentally produced amounts of activities of the two radioisotopes, irradiated at identical conditions, were compared and found to be in good agreement. Based on the various tests, radiological safety analysis and standardization of the irradiation procedure, necessary approval was obtained from the competent reactor operating and safety authorities for regular production of gaseous radiotracers in DHRUVA reactor.

Studies on the development of ¹69Yb-brachytherapy seeds: New generation brachytherapy sources for the management of cancer.

This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm (ϕ) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES. Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74 MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the potential for use in prostate brachytherapy. A protocol to prepare (169)Yb-brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets was also formulated.

Practicality of production of ³²P by direct neutron activation for its utilization in bone pain palliation as Na3[³²P]PO4.

Large-scale production of ³²P for its clinical use in palliative care of painful bone metastasis in the form of Na3[³²P]PO4 (³²P-sodium orthophosphate) has been practiced for six decades. The classical route of production of ³²P by (n,p) reaction on high purity elemental sulfur yields no-carrier-added (NCA) ³²P. Since high specific activity ³²P is not essential for the formulation of Na3[³²P]PO4 for bone pain palliation, an alternate route of production of ³²P by direct neutron capture using elemental phosphorus target [(31)P(n,γ)³²P] was envisaged and its suitability for use in bone pain palliation was evaluated. Toward this, irradiation of elemental red phosphorus target was carried out at a neutron flux of 8×10¹³ n/cm².s for 60 days and this yielded ³²P with a specific activity of 230±15 MBq/mg (6.2±0.4 mCi/mg) having >99.9% radionuclidic purity. About 370-555 MBq (10-15 mCi) doses of Na3[³²P]PO4 were formulated in sterile saline (pH 7.4) using the ³²P produced. The radiochemical purity of the formulation was found to be ~99% with respect to PO4³â». The formulation exhibited good in vitro stability in saline and in human serum. Biodistribution studies carried out in normal Wistar rats revealed comparable pharmacokinetic properties of the formulation prepared using (n,γ) produced ³²P with that of NCA ³²P produced by (n,p) route. Besides having the advantages of simplicity in radiochemical processing and minimum radioactive waste generation, use of the proposed production route in place of the traditional ³²S(n,p)³²P route would result in better utilization of irradiation volume of research reactors.