Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route

Abstract

IntroductionThe scope of using no carrier added (NCA) 90Y [T1/2=64.1h, Eβ(max)=2.28MeV] obtained from 90Sr/90Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using 90Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. MethodsYttrium-90 was produced by thermal neutron irradiation of Y2O3 target at a neutron flux of ~1×1014 n/cm2.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 90Y labeled hydroxyapatite (HA) using HA particles of 1–10μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of 90Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of 90Y-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 185MBq 90Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. ResultsYttrium-90 was produced with a specific activity of 851±111MBq/mg and radionuclidic purity of 99.95±0.02%. 90Y-labeled HA particles (185±10MBq 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 90Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using 90Y produced via (n,γ) route in the management of the disease. ConclusionThe studies revealed that effective utilization of 90Y produced via (n,γ) route in a medium flux research reactor coupled with the developed strategy of using HA kits for convenient formulation of 90Y-HA at the hospital radiopharmacy can contribute to sustainable growth in the clinical utilization of 90Y in RSV in the foreseeable future.