Formulation of ‘ready-to-use’ human clinical doses of 177Lu-labeled bisphosphonate amide of DOTA using moderate specific activity 177Lu and its preliminary evaluation in human patient

Abstract

Abstract Radiolabeled macrocyclic bisphosphonate ligands have recently been demonstrated to be highly efficacious in treatment of patients with painful bone metastases. Herein, we report a robust protocol for formulation of therapeutically relevant doses of 177Lu-labeled bisphosphonate amide of DOTA (BPAMD) using moderate specific activity 177Lu produced by direct (n,γ) route and its preliminary investigation in human patients. Doses (2.8 ± 0.2 GBq) were formulated with high radiochemical purity (98.3 ± 0.4 %) using a protocol optimized after extensive radiochemical studies. In vitro binding studies with mineralized osteosarcoma cells demonstrated specific binding of the radiotracer. Biodistribution studies in healthy Wistar rats demonstrated rapid skeletal accumulation with fast clearance from the non-target organs. In a patient administered with 555 MBq dose of 177Lu-BPAMD, intense radiotracer uptake was observed in the metastatic skeletal lesions with insignificant uptake in any other major non-targeted organs. Preliminary clinical investigations carried out after administration of 2.6 GBq of 177Lu-BPAMD revealed significant reduction in pain after 1 week without any adverse effects. The developed protocol for formulation of 177Lu-BPAMD doses using moderate specific activity carrier added 177Lu has been found to be effective and warrants wider investigations in patients with painful skeletal metastases.