177Lu-DOTA-lanreotide:: A novel tracer as a targeted agent for tumor therapy

Lu-177 of specific activity similar to 100-110 TBq/g and radionuclidic purity of similar to 100% was obtained by irradiation of enriched Lu2O3 (60.6% Lu-176) target for 7 days at a thermal neutron flux of 3 x 10(13) n/cm(2)/sec. The Lu-177 labeling of a macrocyclic bifunctional chelating agent viz. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has been extensively studied. Lanreotide, [beta-naphthyl-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2] a disulfide-linked cyclic octapeptide and a somatostatin analog, reported to bind with a wide variety of tumors expressing somatostatin receptors, was conjugated with DOTA. The peptide-BFCA conjugate was characterized with the help of high-resolution two-dimensional proton NMR spectroscopy. The Lu-177 labeling of the DOTA-lanreotide conjugate has been standardized to give a radiolabeling yield of 85%. The tracer showed specific binding with A-431 human epidermoid carcinoma and IMR-32 human brain neuroblastoma cells. (C) 2004 Elsevier Inc. All rights reserved.