Abstract
Numerous peptide receptors have recently been reported to be expressed or overexpressed in various human cancers. For instance, somatostatin receptors are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP-NET), including both primaries and metastases. The density is often high, and the distribution is usually homogenous. While various somatostatin receptor subtypes can be expressed in these tumors, the sst2 is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with octreotide in hormone-secreting GEP-NET, in vivo diagnostic with radiolabeled diethylene triamine pentaacetic acid octreotide (Octreoscan) to evaluate the extend of the disease, and 90Y- or 177Lu-[90Y-DOTA]-d-Phe1-Tyr3 octreotide radiotherapy. GEP-NET can, however, express peptide receptors other than somatostatin receptor: Insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors; gastrinomas express very high levels of secretin receptors. GEP-NET may also express cholecystokinin 2, bombesin, neuropeptide Y, or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP-NET, providing a molecular basis for in vivo multireceptor targeting of those tumors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Behr TM, Jenner N, Behe M, Angerstein C, Gratz S, Raue F, Becker W (1999) Radiolabeled peptides for targeting cholecystokinin-B/gastrin receptor-expressing tumors. J Nucl Med 40:1029–1044
Buchegger F, Bonvin F, Kosinski M, Schaffland AO, Prior J, Reubi JC, Blauenstein P, Tourwe D, Garcia Garayoa E, Bischof Delaloye A (2003) Radiolabeled neurotensin analog, (99m)Tc-NT-XI, evaluated in ductal pancreatic adenocarcinoma patients. J Nucl Med 44:1649–1654
de Jong M, Breeman WA, Bernard BF, Bakker WH, Visser TJ, Kooij PP, van Gameren A, Krenning EP (2001) Tumor response after [(90)Y-DOTA(0),Tyr(3)]-octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size. J Nucl Med 42:1841–1846
Ding WQ, Cheng ZJ, McElhiney J, Kuntz SM, Miller LJ (2002) Silencing of secretin receptor function by dimerization with a misspliced variant secretin receptor in ductal pancreatic adenocarcinoma. Cancer Res 62:5223–5229
Frucht H, Howard JM, Slaff JI, Wank SA, McCarthy DM, Maton PN, Vinayek R, Gardner JD, Jensen RT (1989) Secretin and calcium provocative tests in the Zollinger-Ellison syndrome. A prospective study. Ann Intern Med 111:713–722
Gibril F, Reynolds JC, Doppman JL, Chen CC, Venzon DJ, Termanini B, Weber HC, Stewart CA, Jensen RT (1996) Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. Ann Intern Med 125:26–34
Korner M, Eltschinger V, Waser B, Schonbrunn A, Reubi JC (2005) Value of immunohistochemistry for somatostatin receptor subtype sst2A in cancer tissues: lessons from the comparison of anti-sst2A antibodies with somatostatin receptor autoradiography. Am J Surg Pathol 29:1642–1651
Korner M, Hayes GM, Rehmann R, Zimmermann A, Friess H, Miller LJ, Reubi JC (2005) Secretin receptors in normal and diseased human pancreas: marked reduction of receptor binding in ductal neoplasia. Am J Pathol 167:959–968
Kvols LK, Reubi JC (1993) Metastatic carcinoid tumors and the malignant carcinoid syndrome. Acta Oncol 32:197–201
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJM, Kooij PP, Herder WW, Feelders RA, Eijck CHJ, Jong M, Srinivasan A, Erion JL, Krenning EP (2003) Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med 30:417–422
Kwekkeboom DJ, Bakker WH, Kooij PP, Erion J, Srinivasan A, de Jong M, Reubi JC, Krenning EP (2000) Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in patients with medullary thyroid carcinoma. Eur J Nucl Med 27:1312–1317
Kwekkeboom DJ, Krenning EP, de Jong M (2000) Peptide receptor imaging and therapy. J Nucl Med 41:1704–1713
Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ (1996) Octreotide. N Engl J Med 334:246–254
Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, Bartolomei M, Orsi F, De Cicco C, Macke HR, Chinol M, de Braud F (2001) Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med 28:426–434
Reubi JC (2003) Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 24:389–427
Reubi JC, Kappeler A, Waser B, Laissue JA, Hipkin RW, Schonbrunn A (1998) Immunohistochemical localization of somatostatin receptors sst2A in human tumors. Am J Pathol 153:233–245
Reubi JC, Kvols LK, Waser B, Nagorney D, Heitz PU, Charboneau JW, Reading CC, Moertel C (1990) Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 50:5969–5977
Reubi JC, Waser B (2003) Concomitant expression of several peptide receptors in neuroendocrine tumors as molecular basis for in vivo multireceptor tumor targeting. Eur J Nucl Med 30:781–793
Reubi JC, Waser B, Schaer JC, Laissue JA (1999) Neurotensin receptors in human neoplasms: high incidence in Ewing sarcomas. Int J Cancer 82:213–218
Reubi JC, Waser B, Vale W, Rivier J (2003) Expression of CRF1 and CRF2 receptors in human cancers. J Clin Endocrinol Metab 88:3312–3320
Schulz S, Pauli SU, Schulz S, Handel M, Dietzmann K, Firsching R, Hollt V (2000) Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A. Clin Cancer Res 6:1865–1874
Scopinaro F, De Vincentis G, Varvarigou AD, Laurenti C, Iori F, Remediani S, Chiarini S, Stella S (2003) 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. Eur J Nucl Med Mol Imaging 30:1378–1382
Valkema R, Jamar F, Jonard P, Bakker WH, Norenberg J, Hadley J, Smith C, Kvols L, Pauwels S, Krenning EP (2000) Targeted radiotherapy with 90Y-SMT487 (Octreo Ther): a phase 1 study [Abstract]. J Nucl Med 41(Suppl):111P
Van de Wiele C, Dumont F, Vanden Broecke R, Oosterlinck W, Cocquyt V, Serreyn R, Peers S, Thornback J, Slegers G, Dierckx RA (2000) Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med 27:1694–1699
Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J (2001) The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 12:941–945
Conflict of interest statement
We declare that we have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Reubi, J.C. Peptide receptor expression in GEP-NET. Virchows Arch 451 (Suppl 1), 47–50 (2007). https://doi.org/10.1007/s00428-007-0443-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-007-0443-2