Imaging tumors with peptide-based radioligands

Regulatory peptides are small, readily diffusable and potent natural substa nces with a wide spectrum of receptor-mediated actions in humans. High affi nity receptors for these peptides are (over-) expressed in many neoplasms, and these receptors may represent, therefore, new molecular targets for can cer diagnosis and therapy. This review aims to give an overview of the pept ide-based radiopharmaceuticals which are presently already commercially ava ilable or which are in advanced stages of their clinical testing so that th eir broader availability is anticipated soon. Physiologically, these peptid es bind to and act through G protein-coupled receptors in the cell membrane . Historically, somatostatin analogs are the first class of receptor bindin g peptides having gained clinical application. In-111-DTPA-[D-Phe(1)]-octre otide is the first and only radiopeptide which has obtained regulatory appr oval in Europe and the United States to date. Extensive clinical studies in volving several thousands of patients have shown that the major clinical ap plication of somatostatin receptor scintigraphy is the detection and the st aging of gastroenteropancreatic neuroendocrine tumors (carcinoids). In thes e tumors, octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent neoplasms is limited Radio-labeled vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal adenocarcinomas, as well as som e neuroendocrine tumors, including insulinomas (the latter being often miss ed by somatostatin receptor scintigraphy). Due to the outstanding diagnosti c accuracy of the pentagastrin test in detecting the presence, persistence, or recurrence of medullary thyroid cancer (MTC), we postulated the express ion of the corresponding (i.e. cholecystokinin [CCK-] -B) receptor type in human MTC. This receptor is also widely expressed on human small-cell lung cancer. Indeed, In-111-labeled DTPA derivatives of gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands, e.g. among many others, gast rin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or gluc agonlike peptide-1 (glp-1) analogs (the latter for the specific detection o f insulinomas), is currently under development. Summarizing, radiolabeled r egulatory peptides have opened new horizons in nuclear oncology for diagnos is (and potential internal radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful peptide-based ra dioligands.