Preparation and preliminary studies on ¹⁷⁷Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer

Abstract 

Introduction

Intra-arterial administration of particulates labeled with suitable β⁻-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. ¹⁷⁷Lu [T_1/2=6.73 d, E_β(max)=0.49 MeV, E_γ=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20–60 μm size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides.

Methods

¹⁷⁷Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of ¹⁷⁷Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats.

Results

¹⁷⁷Lu was produced with a specific activity of 444.2±41.8 GBq/mg and radionuclidic purity of 99.98%. ¹⁷⁷Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited ∼73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies.

Conclusion

¹⁷⁷Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

Keywords: ¹⁷⁷Lu, Hydroxyapatite, Liver cancer, Intra-arterial radionuclide therapy, Radiolabeled microspheres/particulates