Y-90 AND IN-111 LABELING, RECEPTOR-BINDING AND BIODISTRIBUTION OF [DOTA(0),D-PHE(1),TYR(3)]OCTREOTIDE, A PROMISING SOMATOSTATIN ANALOG FOR RADIONUCLIDE THERAPY

In vitro octreotide receptor binding of [(111)]In-DOTA(0),D-Phe(1),Tyr (3)] octreotide (In-111-DOTATOC) and the in vivo metabolism of Y-90- o r In-111-labelled DOTATOC were investigated in rats in comparison with [In-111-DTPA(0)]octreotide [In-111-DTPAOC). In-111-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide re ceptor in rat cerebral cortex microsomes. Twenty-four hours after inje ction of Y-90- or In-111-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrena ls and tumour was a factor of 2-6 that after injection of In-111-DTPAO C. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tum our was almost completely blocked by pretreatment with 0.5 mg unlabell ed octreotide, indicating specific binding to the octreotide receptors . These findings strongly indicate that Y-90-DOTATOC is a promising ra diopharmaceutical for radiotherapy and that In-111-DOTATOC is of poten tial value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.