COMPARATIVE-STUDIES ON THE EXPRESSION OF SOMATOSTATIN RECEPTOR SUBTYPES, OUTCOME OF OCTREOTIDE SCINTIGRAPHY AND RESPONSE TO OCTREOTIDE TREATMENT IN PATIENTS WITH CARCINOID-TUMORS

We have compared the expression of somatostatin receptor (sstr) subtyp es with the outcome of somatostatin receptor scintigraphy and the effe ct of somatostatin receptor activation in patients with disseminated c arcinoid tumours. Tumour tissues from nine patients with midgut carcin oids (ileal) and three patients with foregut carcinoids (gastric, thym ic) were analysed using Northern blotting, Expression of somatostatin receptors was demonstrated in ail tumours (12 out of 12), with ail fiv e receptor subtypes present in 9 out of 12 tumours, Somatostatin recep tor scintigraphy using [In-111]DTPA-D-Phe(1)-octreotide visualized tum ours in all patients (12 out of 12). The In-111 activity concentration s in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B In-111 activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in mark ed symptom relief accompanied by a significant reduction in tumour mar kers, for example urinary-5-HIAA levels (28-71% reduction). incubation of midgut carcinoid tumours in primary culture with octreotide (10 mu M) resulted in a reduction in spontaneously secreted serotonin (45-71 % reduction) and 5-HIAA (41-94% reduction). The results demonstrate th at carcinoid tumours possess multiple somatostatin receptor subtypes a nd that somatostatin analogues such as octreotide, which preferentiall y bind to somatostatin receptor subtype 2 and 5, can be used in the di agnosis and medical treatment of these tumours. In the future, novel s omatostatin analogues with subtype specific receptor profiles may prov e to be oi value for individualizing the treatment of disseminated car cinoid tumour disease.