Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA(0),D-Phe(1),Tyr(3)]octreotide, a promising somatostatin analogue 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- or 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 receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of Y-90- or In-111-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of In-111-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that Y-90-DOTATOC is a promising radiopharmaceutical for radiotherapy and that In-111-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.