title: Evaluation of somatostatin receptors in human cancer.
abstract: The binding of 123I-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, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 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 123I-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 123I-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 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.
authors.affiliation: Department of Nuclear Medicine, University of Vienna.
authors.forename: T
authors.initials: T
authors.lastname: Pantev
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: N
authors.initials: N
authors.lastname: Neuhold
authors.forename: P
authors.initials: P
authors.lastname: Angelberger
authors.forename: A
authors.initials: A
authors.lastname: Luger
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
mesh_terms: D000236:Adenoma / Q000000981:diagnostic imaging; D001667:Binding, Competitive / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000000981:diagnostic imaging*; D015282:Octreotide / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000502:physiology; D017481:Receptors, Somatostatin; D015899:Tomography, Emission-Computed, Single-Photon; D014407:Tumor Cells, Cultured / Q000000981:diagnostic imaging*
chemical_list: D014408:Biomarkers, Tumor; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; C062646:SDZ 204-090; D015282:Octreotide