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111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours
S H Hashemi1, S-A Benjegård, H Ahlman
1Lundberg Laboratory for Cancer Research at the Department of Pathology, Göteborg University, Göteborg, Sweden.
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.
Conclusion:
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.