title: Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route.
abstract: BACKGROUND
  The scope of using no carrier added (NCA) (90)Y [T(1/2) = 64.1 h, Eβ(max) = 2.28 MeV] obtained from (90)Sr/(90)Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using (90)Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored.
  
  
  METHODS
  Yttrium-90 was produced by thermal neutron irradiation of Y(2)O(3) target at a neutron flux of ~1×10(14) n/cm(2).s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of (90)Y labeled hydroxyapatite (HA) using HA particles of 1-10 μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of (90)Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of (90)Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq (90)Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy.
  
  
  RESULTS
  Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. (90)Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (>99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of (90)Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using (90)Y produced via (n,γ) route in the management of the disease.
  
  
  CONCLUSIONS
  The studies revealed that effective utilization of (90)Y produced via (n,γ) route in a medium flux research reactor coupled with the developed strategy of using HA kits for convenient formulation of (90)Y-HA at the hospital radiopharmacy can contribute to sustainable growth in the clinical utilization of (90)Y in RSV in the foreseeable future.
authors: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: K V
authors: KV
authors: Vimalnath
authors: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, 400085, India. Electronic address: sudipta@barc.gov.in.
authors: Sudipta
authors: S
authors: Chakraborty
authors: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: A
authors: A
authors: Rajeswari
authors: Radiation Biology Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: H D
authors: HD
authors: Sarma
authors: Chemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: Jitendra
authors: J
authors: Nuwad
authors: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: Usha
authors: U
authors: Pandey
authors: Nuclear Medicine and PET Services, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital, Coimbatore, 641014, India.
authors: K
authors: K
authors: Kamaleshwaran
authors: Nuclear Medicine and PET Services, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital, Coimbatore, 641014, India.
authors: Ajit
authors: A
authors: Shinto
authors: Isotope Production and Applications Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors: Ashutosh
authors: A
authors: Dash
mesh_terms: D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical; D017886:Durapatite / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000737:chemistry*
chemical_list: D015021:Yttrium Radioisotopes; D017886:Durapatite
keywords: (90)Y; (n,γ) production; Hydroxyapatite (HA); Kit formulation; Radiation synovectomy (RSV)