Regulatory
peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for these
peptides are (over-) expressed in many
neoplasms, and these receptors may represent, therefore, new molecular targets for
cancer diagnosis and
therapy. This review aims to give an overview of the
peptide-based
radiopharmaceuticals which are presently already commercially available or which are in advanced stages of their clinical testing so that their broader availability is anticipated soon. Physiologically, these
peptides bind to and act through
G protein-coupled receptors in the cell membrane. Historically,
somatostatin analogs are the first class of receptor binding
peptides having gained clinical application. 111In-
DTPA-[D-Phe1]-
octreotide is the first and only radiopeptide which has obtained regulatory approval in Europe and the United States to date. Extensive clinical studies involving several thousands of patients have shown that the major clinical application of
somatostatin receptor scintigraphy is the detection and the staging of gastroenteropancreatic
neuroendocrine tumors (
carcinoids). In these
tumors,
octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent
neoplasms is limited. Radiolabeled
vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal
adenocarcinomas, as well as some
neuroendocrine tumors, including
insulinomas (the latter being often missed by
somatostatin receptor scintigraphy). Due to the outstanding diagnostic accuracy of the
pentagastrin test in detecting the presence, persistence, or recurrence of
medullary thyroid cancer (MTC), we postulated the expression of the corresponding (ie.
cholecystokinin [
CCK-] -B) receptor type in human MTC. This receptor is also widely expressed on human
small-cell lung cancer. Indeed, 111In-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,
gastrin-releasing peptide/
bombesin,
neurotensin,
substance-P, pan-
somatostatin (
somatostatin derivatives which bind to all five receptor subtypes) or
glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of
insulinomas), is currently under development. Summarizing, radiolabeled regulatory
peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal
radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful
peptide-based radioligands.