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Somatostatin Receptor Subtypes in Human Pheochromocytoma: Subcellular Expression Pattern and Functional Relevance for Octreotide Scintigraphy

Departments of Endocrinology and Metabolism (J.M., N.U., H.L.), Pharmacology and Toxicology (St.S., V.H.), Obstetrics and Gynecology (So.S.), and Nuclear Medicine (J.M., R.S.), Otto-von-Guericke-University, D-39120 Magdeburg, Germany

Address all correspondence and requests for reprints to: Prof. Dr. Hendrik Lehnert Department of Endocrinology and Metabolism University Hospital of Magdeburg Leipziger Strasse 44, D-39120 Magdeburg, Germany. E-mail: hendrik.lehnert{at}medizin.uni-magdeburg.de.

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. In pheochromocytoma, data on somatostatin receptor subtyping have thus far been sparse. Pheochromocytomas often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. Here, we have examined somatostatin receptor protein expression in a panel of 52 pheochromocytomas from 35 randomly selected patients by immunostaining with specific polyclonal anti-sst_1–5 and monoclonal mouse anti-SS-14 antibodies. Staining pattern, distribution and subcellular localization of somatostatin receptor subtypes were investigated. Seventeen patients received ¹¹¹In-octreotide scintigraphy. Although the vast majority of tumors (90%) showed positive immunohistochemical staining for sst₃, immunoreactive sst_2A receptors were only seen in 13 tumors (25%). All other somatostatin receptor subtypes were less frequently detected. Interestingly, among sst₃-positive tumors strikingly different subcellular distributions of immunoreactive sst₃ receptors were observed. In most cases, immunoreactive sst₃ receptors were distributed throughout the cytosol. Scintigraphic localization of tumors larger than 1 cm in diameter was always successful in the presence of immunoreactive sst_2A receptors. In the absence of sst_2A, true-positive octreotide scintigraphy was only seen in the presence of membrane-associated sst₃ immunoreactivity. Our findings suggest that selective expression of functional membrane-associated sst₃ receptors is sufficient for high tracer uptake during octreotide scintigraphy in a subgroup of human pheochromocytomas. These tumors may represent a potential target treatment with somatostatin receptor agonists with improved sst₃ activity.

This work was supported by Deutsche Forschungsgemeinschaft Grants SCHU 1332/2-1 (So.S.) and SCHU 924/4–3 (St.S.).

J.M. and N.U. contributed equally to this work.

Abbreviations: DAB, Diaminobenzidine; HEK, human embryonic kidney; MIBG, metaiodobenzylguanidine; RT, room temperature.

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