Preparation and preliminary biological evaluation of a 177Lu labeled sanazole derivative for possible use in targeting tumor hypoxia

The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therapeutic radioisotope viz. Lu-177 is described. The nitroimidazole used for the present study is [N-2'(carboxyethyl)-2-(3'-nitro-1'-triazolyi)acetamide], the carboxylic acid derivative of sanazole, which possesses an optimal combination of desired properties such as, selective toxicity for hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4'-aminobenzylacetamido)-cyclododecane-4,7,10- triacetic acid (p-amino-DOTA-anilide). Lu-177 was produced in adequate specific activity (110TBq/g) and high radionuclidic purity (similar to100%) by irradiating enriched (60.6% Lu-176) Lu2O3 target and used for radiolabeling of the sanazole-BFCA conjugate. similar to98% Complexation yield was achieved under optimized conditions. The complex has been characterized by paper chromatography and HPLC studies. Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate tumor uptake (0.880%/g at 1 h post-injection) with favorable tumor to blood (4.00 at 1 h post-injection) and tumor to muscle (4.63 at 1 h post-injection) ratios. (C) 2004 Elsevier Ltd. All rights reserved.