title: Palliative care of bone pain due to skeletal metastases: Exploring newer avenues using neutron activated (45)Ca.
abstract: BACKGROUND
  With 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 (45)Ca (t½=163 days, Eβmax=0.3MeV) using moderate flux research reactor, its purification from radionuclidic impurities adopting electrochemical approach and preclinical evaluation of (45)CaCl2.
  
  
  METHODS
  Irradiation parameters were optimized by theoretical calculations for production of (45)Ca 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 (44)Ca) CaO target at a thermal neutron flux of ~1 × 10(14) n.cm(-2).s(-1) for 4 months. Scandium-46 impurity co-produced along with (45)Ca was efficiently removed adopting an electrochemical separation approach. The bone specificity of (45)CaCl2 was established by in vitro studies involving its uptake in hydroxyapatite (HA) particles and also evaluating its biodistribution pattern over a period of 2 weeks after in vivo administration in Wistar rats.
  
  
  RESULTS
  Thermal neutron irradiation of 100mg of enriched (98% in (44)Ca) CaO target followed by radiochemical processing and electrochemical purification procedure yielded ~37 GBq of (45)Ca with a specific activity of ~370 MBq/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 (45)CaCl2 (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 2 weeks.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first study on utilization of (45)CaCl2 in the context of nuclear medicine. The results obtained in this study hold promise and warrant further investigations for future translation of (45)CaCl2 to the clinics, thereby potentially enabling a cost-effective approach for metastatic bone pain palliation especially in developing countries.
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India. Electronic address: rubelc@barc.gov.in.
authors.forename: Rubel
authors.initials: R
authors.lastname: Chakravarty
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Ramu
authors.initials: R
authors.lastname: Ram
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: K Viswanathan Vimalnath
authors.initials: KV
authors.lastname: Nair
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Ardhi
authors.initials: A
authors.lastname: Rajeswari
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Haladhar Dev
authors.initials: HD
authors.lastname: Sarma
authors.affiliation: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India. Electronic address: adash@barc.gov.in.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000556:secondary*; D002122:Calcium Chloride / Q000737:chemistry; D002132:Calcium Radioisotopes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017886:Durapatite / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009502:Neutrons / Q000627:therapeutic use*; D010146:Pain / Q000150:complications*; D059408:Pain Management / Q000379:methods*; D010166:Palliative Care / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D017208:Rats, Wistar; D013326:Strontium Radioisotopes / Q000737:chemistry
chemical_list: D002132:Calcium Radioisotopes; D013326:Strontium Radioisotopes; D017886:Durapatite; D002122:Calcium Chloride
keywords: (45)Ca; Bone pain palliation; Electroamalgamation; Neutron activation; Radionuclidic impurity