Comparison of 1 ! 1 In-labeled Somatostatin Analogues for Tumor Scintigraphy and Radionuclide Therapy 1

We evaluated the following '"In-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, Oil'A: tetraazacyclododecanetetraacetic acid, DOTA): [DTPA°loctreotide, |DTPA",Tyr'loctreotide, [DTPA°,D-Tyr'loctreotide. |DTPA°,Tyr']octreotate (Thr(ol) in octreotide replaced with Thr|, and [DOTA°,Tyr'loctreotide, in vitro and in vivo. In vitro, all compounds .showed high and specific binding to SS recep tors in mouse pituitary AtT20 tumor cell membranes, and K '.,,,s were in the nanomolar range. Furthermore, all compounds showed specific internalization in rat pancreatic tumor cells; uptake of |'"lnDTPA",Tyr*]octreotate was the highest of the compounds tested, and that of |l"ln-DTPA0,l)-Tyr'loctreotide was the lowest. Biodistribution exper iments in rats showed that, 4, 24, and 48 h after injection of |'"lnDTPA°,Tyr']octreotide, |mIn-DTPA0.Tyr3loctreotate, and ('"InDOTA°,Tyr'loctreotide, radioactivity in the octreotide-binding, receptorexpressing tissues and tumor-to-blood ratios were significantly higher than those after injection of ["'In-DTPA"]octreotide. Uptake of l'"lnDTPA°,Tyr']octreotate in the target organs was also, in vivo, the highest of the radiolabeled peptides tested, whereas that of ['"in-DTPA",!)Tyr'loctreotide was the lowest. Uptake of |"'ln-DTPA",Tyr*loctreotide, ['"ln-DTPA",TyrJloctreotate, and ['"ln-DOTA0,TyrJloctreotide in tar get tissues was blocked by >90% by 0.5 mg of unlabeled octreotide, indicating specific binding to the octreotide receptors. Blockade of ['"InDTPA°,D-Tyr'loctreotide was >70%. In conclusion, radiolabeled [DTPA°,Tyr<loctreotide and, especially, (DTPA",Tyr'|octreotate and their DOTA-coupled counterparts are most promising for scintigraphy and radionuclide therapy of SS receptor-positive tumors in humans.