Somatostatin receptors are expressed in selected human cancers. They are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP NET), including both primaries and metastases. The density is often high, the distribution is usually homogeneous. While various somatostatin receptor subtypes can be expressed in these tumors, sst2 is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with cold octreotide in hormone-secreting GEP NET, in vivo diagnostic with Octreoscan to evaluate the extend of the disease, and 90Y-DOTATOC radiotherapy. GEP NET can, however, express peptide receptors other than somatostatin receptors: insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors, gut NET (carcinoids) may also express cholecystokinin 2, bombesin 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.

Keywords:
Somatostatin, Regulatory peptides, Glucagon-like peptide 1, Cholecystokinin, Receptor co-expression, Receptor autoradiography, Peptide receptor targeting, Bombesin, Vasoactive intestinal peptide
1.
Reubi JC: Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24:389–427.
2.
Kwekkeboom DJ, Krenning EP, de Jong M: Peptide receptor imaging and therapy. J Nucl Med 2000;41:1704–1713.
3.
Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ: Octreotide. N Engl J Med 1996;334:246–254.
4.
Gibril F, Reynolds JC, Doppman JL, Chen CC, Venzon DJ, Termanini B, Weber HC, Stewart CA, Jensen RT: Somatostatin receptor scintigraphy: Its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. Ann Intern Med 1996;125:26–34.
5.
Valkema R, Jamar F, Jonard P, Bakker WH, Norenberg J, Hadley J, Smith C, Kvols L, Pauwels S, Krenning EP: Targeted radiotherapy with 90Y-SMT487 (Octreo Ther): A phase 1 study (abstract). J Nucl Med 2000;41(suppl):111P.
6.
Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J: 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 2001;12:941–945.
7.
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: Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med 2001;28:426–434.
8.
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJM, Kooij PP, Herder WW, Feelders RA, Eijck CHJ, Jong M, Srinivasan A, Erion JL, Krenning EP: Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med Mol Imaging 2003;30:417–422.
9.
Scopinaro F, De Vincentis G, Varvarigou AD, Laurenti C, Iori F, Remediani S, Chiarini S, Stella S: 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. Eur J Nucl Med Mol Imaging 2003;30:1378–1382.
10.
Van de Wiele C, Dumont F, Vanden Broecke R, Oosterlinck W, Cocquyt V, Serreyn R, Peers S, Thornback J, Slegers G, Dierckx RA: Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: A feasibility study. Eur J Nucl Med 2000;27:1694–1699.
11.
Behr TM, Jenner N, Behe M, Angerstein C, Gratz S, Raue F, Becker W: Radiolabeled peptides for targeting cholecystokinin-B/gastrin receptor-expressing tumors. J Nucl Med 1999;40:1029–1044.
12.
Kwekkeboom DJ, Bakker WH, Kooij PP, Erion J, Srinivasan A, de Jong M, Reubi JC, Krenning EP: Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in patients with medullary thyroid carcinoma. Eur J Nucl Med 2000;27:1312–1317.
13.
Buchegger F, Bonvin F, Kosinski M, Schaffland AO, Prior J, Reubi JC, Blauenstein P, Tourwe D, Garcia Garayoa E, Bischof Delaloye A: Radiolabeled neurotensin analog, (99m)Tc-NT-XI, evaluated in ductal pancreatic adenocarcinoma patients. J Nucl Med 2003;44:1649–1654.
14.
Reubi JC, Waser B: Concomitant expression of several peptide receptors in neuroendocrine tumors as molecular basis for in vivo multireceptor tumor targeting. Eur J Nucl Med 2003;30:781–793.
15.
Reubi JC, Kappeler A, Waser B, Laissue JA, Hipkin RW, Schonbrunn A: Immunohistochemical localization of somatostatin receptors sst2A in human tumors. Am J Pathol 1998;153:233–245.
16.
Reubi JC, Kvols LK, Waser B, Nagorney D, Heitz PU, Charboneau JW, Reading CC, Moertel C: Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 1990;50:5969–5977.
17.
Kvols LK, Reubi JC: Metastatic carcinoid tumors and the malignant carcinoid syndrome. Acta Oncol 1993;32:197–201.
18.
Schulz S, Pauli SU, Schulz S, Handel M, Dietzmann K, Firsching R, Hollt V: Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A. Clin Cancer Res 2000;6:1865–1874.
19.
de Jong M, Breeman WA, Bernard BF, Bakker WH, Visser TJ, Kooij PP, van Gameren A, Krenning EP: 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 2001;42:1841–1846.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.