Palliative care of bone pain due to skeletal metastases: Exploring newer avenues using neutron activated 45Ca

Abstract

IntroductionWith an objective to develop a cost-effective radiochemical formulation for palliation of pain due to skeletal metastases, we have demonstrated a viable method for large-scale production of 45Ca (t½=163days, Eβmax=0.3MeV) using moderate flux research reactor, its purification from radionuclidic impurities adopting electrochemical approach and preclinical evaluation of 45CaCl2. MethodsIrradiation parameters were optimized by theoretical calculations for production of 45Ca with highest possible specific activity along with minimum radionuclidic impurity burden. Based on this, the radioisotope was produced in reactor by irradiation of isotopically enriched (98% in 44Ca) CaO target at a thermal neutron flux of ~1×1014 n.cm−2.s−1 for 4months. Scandium-46 impurity co-produced along with 45Ca was efficiently removed adopting an electrochemical separation approach. The bone specificity of 45CaCl2 was established by in vitro studies involving its uptake in hydroxyapatite (HA) particles and also evaluating its biodistribution pattern over a period of 2weeks after in vivo administration in Wistar rats. ResultsThermal neutron irradiation of 100mg of enriched (98% in 44Ca) CaO target followed by radiochemical processing and electrochemical purification procedure yielded ~37GBq of 45Ca with a specific activity of ~370MBq/mg and radionuclidic purity>99.99%. The reliability and reproducibility of this approach were amply demonstrated by process demonstration in several batches. In vitro studies indicated significant uptake of 45CaCl2 (up to 65%) in HA particles. In vivo biodistribution studies in Wistar rats showed specific skeletal accumulation (40–46%ID) with good retention over a period of 2weeks. ConclusionsTo the best of our knowledge, this is the first study on utilization of 45CaCl2 in the context of nuclear medicine. The results obtained in this study hold promise and warrant further investigations for future translation of 45CaCl2 to the clinics, thereby potentially enabling a cost-effective approach for metastatic bone pain palliation especially in developing countries.