Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.
We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.
Nilsson
O
O
Department of Pathology, Sahlgrenska University Hospital, University of Gothenburg, Göteborg, Sweden.
Kölby
L
L
Wängberg
B
B
Wigander
A
A
Billig
H
H
William-Olsson
L
L
Fjälling
M
M
Forssell-Aronsson
E
E
Ahlman
H
H
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007078:Ileal Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D015282:Octreotide / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D013953:Thymus Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D005765:Gastrointestinal Agents; D007205:Indium Radioisotopes; D009363:Neoplasm Proteins; D017481:Receptors, Somatostatin; D015282:Octreotide