111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours.
BACKGROUND
The aim of this study was to investigate the importance of somatostatin receptor subtype 2 (SSTR2) expression for 111In-labelled diethylenetriamine-pentaacetic acid (DTPA)-D-Phe1-octreotide binding and uptake of 111In in neuroendocrine tumours.


METHODS
111In activity concentrations in surgical biopsies from neuroendocrine tumours (midgut carcinoid and medullary thyroid carcinoma), breast carcinoma and blood were determined 1-8 days after intravenous injection of 111In-labelled DTPA-D-Phe1-octreotide (140-350 MBq). The ratio of 111In activity concentrations between tumour tissue and blood (T/B value) was calculated. The expression of SSTR2 messenger RNA (mRNA) in tumour biopsies was quantitated by ribonuclease protection assay and SSTR2 protein was localized by immunocytochemistry.


RESULTS
T/B values were highest for tumour biopsies from midgut carcinoids (mean 160 (range 4-1200); n = 65) followed by medullary thyroid carcinoma (mean 38 (range 2-350); n = 88) and breast carcinoma (mean 18 (range 4-41); n = 4). The expression of SSTR2 mRNA (relative to the NCI-H69 cell line) was highest in tumour biopsies from midgut carcinoids (mean 2.5 (range 0.83-6.0); n = 40) followed by medullary thyroid carcinoma (mean 1.3 (range 0.20-6.0); n = 7) and breast carcinoma (mean 0.66 (range 0.29-1.0); n = 9). In tumour biopsies SSTR2 protein was localized exclusively to tumour cells.


CONCLUSIONS
Midgut carcinoid tumours showed a much higher level of SSTR2 expression than medullary thyroid carcinoma in accordance with superior tumour imaging by octreotide scintigraphy. The high SSTR2 mRNA values and T/B values observed in midgut carcinoid tumours were positively correlated.
Hashemi
S H
SH
Lundberg Laboratory for Cancer Research at the Department of Pathology, Göteborg University, Göteborg, Sweden.
Benjegård
S-A
SA
Ahlman
H
H
Wängberg
B
B
Forssell-Aronsson
E
E
Billig
H
H
Nilsson
O
O
D000328:Adult; D000368:Aged; D001706:Biopsy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D002614:Chelating Agents; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism*; D015282:Octreotide / Q000378:metabolism*; D004369:Pentetic Acid; D012333:RNA, Messenger / Q000378:metabolism; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000378:metabolism*
D002614:Chelating Agents; D006728:Hormones; D007205:Indium Radioisotopes; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D004369:Pentetic Acid; D015282:Octreotide