Preparation and preliminary biological evaluation of a 177Lu labeled nitroimidazole derivative for possible use in targeted tumor therapy

Abstract

Summary The preparation and preliminary biological evaluation of a metronidazole-BFCA (bifunctional chelating agent) conjugate labeled with 177Lu is reported. Metronidazole, a well known hypoxia marker has been suitably derivatized and coupled with a polyazamacrocyclic BFCA, namely, para-aminobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-amino-benzyl-DOTA). 177Lu, which is presently being considered as one of the pivotal radionuclides for targeted therapy was produced in adequate specific activity (∼185 TBq/g) and high radionuclidic purity (99.99%) by irradiating enriched (60.6% 176Lu) Lu2O3 target at a moderate thermal neutron flux of 3×1013 n/cm2/s. The metronidazole-BFCA conjugate was radiolabeled with 177Lu in high radiochemical purity (97%). Preliminary biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumors revealed good tumor uptake (1.30% ID/g at 30 min post-injection) with rapid renal clearance (94.48% ID at 30 min post-injection) and significant tumor to blood (28.00 at 3 h post-injection) and tumor to muscle (14.00 at 3 h post-injection) ratios.