COMPARISON OF IN-111-LABELED SOMATOSTATIN ANALOGS FOR TUMOR SCINTIGRAPHY AND RADIONUCLIDE THERAPY

We evaluated the following In-111-labeled somatostatin (SS) analogues (diethylenetriaminepentaacetic acid, DTPA; tetraazacyclododecanetetraa cetic acid, DOTA): [DTPA(0)]octreotide, [DTPA(0),Tyr(3)]octreotide, [D TPA(0),D-Tyr(1)]octreotide, [DTPA(0),Tyr(3)]octreotate [Thr(ol) in oct reotide replaced with Thr], and [DOTA(0),Tyr(3)]octreotide, in vitro a nd in vivo, In vitro, all compounds showed high and specific binding t o SS receptors in mouse pituitary AtT20 tumor cell membranes, and IC(5 0)s were in the nanomolar range, Furthermore, all compounds showed spe cific internalization in rat pancreatic tumor cells; uptake of [(111)I nDTPA(0),Tyr(3)]octreotate was the highest of the compounds tested, an d that of [In-111-DTPA(0),D-Tyr(1)]octreotide was the lowest. Biodistr ibution experiments in rats showed that, 4, 24, and 48 h after injecti on of [(111)InDTPA(0),Tyr(3)]octreotide, [In-111-DTPA(0),Tyr(3)]octreo tate, and [In-111-DOTA(0),Tyr(3)]octreotide, radioactivity in the octr eotide-binding, receptor-expressing tissues and tumor-to-blood ratios were significantly higher than those after injection of [In-111-DTPA(0 )]octreotide. Uptake of [In-111-DTPA(0),Tyr(3)]octreotate in the targe t organs was also, in vivo, the highest of the radiolabeled peptides t ested, whereas that of [In-111-DTPA(0),Tyr(3)]octreotide was the lowes t, Uptake of [In-111-DTPA(0),Tyr(3)]octreotide, [In-111-DTPA(0),Tyr(3) ]octreotate, and [In-111-DOTA(0),Tyr(3)]octreotide in target tissues w as blocked by >90% by 0.5 mg of unlabeled octreotide, indicating speci fic binding to the octreotide receptors. Blockade of [In-111-DTPA(0),D -Tyr(1)]octreotide was >70%. In conclusion, radiolabeled [DTPA(0),Tyr( 3)]octreotide and, especially, [DTPA(0),Tyr(3)]octreotate and their DO TA-coupled counterparts are most promising for scintigraphy and radion uclide therapy of SS receptor-positive tumors in humans.