Synthesis and biological evaluation of 90Y-labeled porphyrin-DOTA conjugate: a potential molecule for targeted tumor therapy.

Abstract

An unsymmetrically substituted porphyrin, 5-[4-(3-amino)-n-propyloxyphenyl]-10,15,20-tris-(4-carboxymethyleneoxyphenyl)porphyrin, was synthesized and coupled with p-NCS-benzyl-DOTA [p-isothiocyanato-benzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid] for exploring its possible potential in targeted tumor therapy. The porphyrin-DOTA conjugate was radiolabeled with 90Y, obtained from a 90Sr/90Y electrochemical generator, developed in-house. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumor showed good tumor uptake (∼3.4% injected activity in per g of tumor) within 30 minutes postinjection. The tumor activity decreased with the progress of time, however, tumor to blood and tumor to muscle ratios considerably increased at 4 days postadministration owing to the clearance of the initially accumulated activities from the nontarget organs. The nonaccumulated activity exhibited major clearance through renal pathway.