EVALUATION OF SOMATOSTATIN RECEPTORS IN HUMAN CANCER

The binding of I-123-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaeochromocytoma, hypophyseal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200-mu-g protein/ml) were incubated with increasing concentrations of I-123-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5-mu-M of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (K(d) 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for I-123-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies I-123-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the I-123-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.