Abstract
We have evaluated the potential usefulness of the radioiodinated octapeptide RC-160, a somatostatin analogue, which might serve as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose, iodine-123 and iodine-125 labelled RC-160 was tested for biological activity and applied in vivo in rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. Our group has recently described the in vivo visualization of such tumours in rats and in humans with the radioiodinated somatostatin analogue [Tyr3]octreotide. Like [123I-Tyr3]octreotide, 123I-RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours. However, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. We therefore conclude that in this animal model 123I-RC-160 has no advantage over [123I-Tyr3]octreotide as a radiopharmaceutical for the in vivo use as a somatostatin receptor imager, although, like [123I-Tyr3]octreotide, 123I-RC-160 shows specific binding to different somatostatin receptor-positive organs. Recently differences were reported in affinity between somatostatin and its analogues for somatostatin receptors expressed in different human cancers, like those of the breast, ovary, exocrine pancreas, prostate and colon. Therefore 123I-RC-160 might be of interest for future use in humans as a radiopharmaceutical for imaging octreotide receptor-negative tumours.
Similar content being viewed by others
References
Reubi JC, Häcki WH, Lamberts SWJ. Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. J Clin Endocrinol Metab 1987;65: 1127–1134
Reubi JC, Maurer R, von Werder K, Torhorst J, Klijn JG, Lamberts SWJ. Somatostatin receptors in human endocrine tumors. Cancer Res 1987;47: 551–558
Reubi JC, Lang W, Maurer R, Koper JW, Lamberts SWJ. Distribution and biochemical characterization of somatostatin receptors in tumors of the human central nervous system. Cancer Res 1987;47:5758–5764
Reubi JC, Kvols LK, Waser B, Nagorney DM, Heitz PU, Charboneau JW, Reading CC, Moertel C. Detection of somatostatin receptors in surgical and percutaneous needle samples of carcinoids and islet cell carcinomas. Cancer Res 1990;50: 5969–5977
Krenning EP, Bakker WH, Breemann WAP, Koper JW, Kooij PPM, Ausema L, Lameris LS, Reubi JC, Lamberts SWJ. Localization of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989;1: 242–244
Bakker WH, Krenning EP, Breemann WAP, Koper JW, Kooij PPM, Reubi JC, Klijn JG, Visser TJ, Doctor R, Lamberts SWJ. Receptor scintigraphy with a radioiodinated somatostatin analogue: radiolabelling, purification, biologic activity, and in vivo application in animals. J Nucl Med 1990;31: 1501–1509
Bakker WH, Krenning EP, Breemann WAP, Kooij PPM, Reubi JC, Koper JW, De Jong M, Lameris JS, Visser TJ, Lamberts SWJ. In vivo use of a radioiodinated somatostatin analogue: dynamics, metabolism and binding to somatostatin receptor-positive tumours in man. J Nucl Med 1991;32: 1184–1189
Lamberts SWJ, Hofland LJ, van Koetsveld PM, Reubi JC, Bruining HA, Bakker WH, Krenning EP. Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic cancers: consequences with regard to diagnosis, localization, and therapy. J Clin Endocrinol Metab 1990; 71: 566–574
Lamberts SWJ, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 1990;323: 1246–1249
Becker W, Marienhagen J, Scheubel R, Saptogino A, Bakker WH, Breeman WAP, Wolf F. Octreotide scintigraphy localizes somatostatin receptor-positive islet carcinomas. Eur J Nucl Med 1991;18:924–927
Faglia G, Bazzani N, Spada A, Arioso M, Ambrosi B, Spinelli F, Sara R, Bonino C, Lungho F. In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([123I] SDZ 204–090). J Clin Endocrinol Metab 1991;73: 850–856
Ur E, Mather SJ, Bomanji J, Ellison D, Britton KE, Grossmann AB, Wass JAH, Besser GM. Pituitary imaging using a labelled somatostatin analogue in acromegaly. Clin Endocrinol 1992;36: 147–150
Reubi JC. New specific radioligand for one subpopulation of brain somatostatin receptors. Life Sci 1985;36: 1829–1836
Srkalovic G, Cai R-Z, Schally AV. Evaluation of receptors for somatostatin in various tumors using different analogs. J Clin endocrinol Metab 1990;70:661–669
Liebow C, Reilly C, Serrano M, Schally AV. Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase. Proc Natl Acad Sci USA 1989;86: 2003–2007
Pinski J, Milovanovic TY, Hamaoui A, Radulovic S, Cai R-Z, Schally AV. Biological activity and receptor binding characteristics to various human tumors of acetylated somatostatin receptors. Proc Soc Exp Biol Med 1992;200:49–56
Poston GJ, Davis N, Schally AV, Schally AM, Gatiaburu J, Guillou PJ. Phase one B study of somatostatin receptor analogue RC-160 in treatment of patients with advanced exocrine pancreatic tumors [Abstract]. Digestion 1990;46: 170
Poston GJ, Schally AV, Schally AM, Guillou PJ. Phase one study on the use and tolerance of somatostatin receptor analogue RC-160 in the treatment of patients with advanted exocrine pancreatic tumors. Gut 1991;32: A342-A344
Reubi JC, Horrisberger U, Essed CE, Jeekel J, Klijn JGM, Lamberts SWJ. Absence of somatostatin receptors in human exocrine pancreatic adenocarcinomas. Gastroenterology 1988;95: 760–763
Maurer R, Reubi JC. Somatostatin receptors in the adrenal. Mol Cell Endocrinol 1986;45: 81–90
Banks WA, Schally AV, Barrera CM, Fasold BM, Durham DA, Csernus VA, Groot K, Ksatin A. Permeability of the murine blood-brain barrier to some octapeptide analogs of somatostatin. Proc Natl Acad Sci USA 1990;87: 6762–6766
Reubi JC, Häcki WH, Lamberts SWJ. Hormone-producing gastrointestinal tumors contain high density of somatostatin receptors. J Clin Endocrinol Metab 1986;63: 433–438
Oosterom R, Verleun T, Zuiderwijk J, Lamberts SWJ. Growth hormone secretion by cultured rat anterior pituitary cells. Effects of culture conditions and dexamethasone. Endocrinology 1983;113: 735–741
Banks WA, Kastin AJ, Radulovic S, Conley FK, Johnson DL, Schally AV Selective uptake of the somatostatin analog RC-160 across the blood-brain barrier of mice with KHT sarcomas. Anticancer Drugs 1992;3: 519–523
Author information
Authors and Affiliations
Additional information
Correspondence to: W.A.P. Breeman, Department of Nuclear Medicine, University Hospital Dijkzigt, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands
The authors wish to thank Dr. Wil Kort, Ineke Hekking-Weyma, Reno Mekes, Marcello Harms and Ina Loeve for their expert assistance during the experiments.
Rights and permissions
About this article
Cite this article
Breeman, W.A.P., Hofland, L.J., Bakker, W.H. et al. Radioiodinated somatostatin analogue RC-160: preparation, biological activity, in vivo application in rats and comparison with [123I-Tyr3]octreotide. Eur J Nucl Med 20, 1089–1094 (1993). https://doi.org/10.1007/BF00173488
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00173488