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Imaging tumors with peptide-based radioligands
T M Behr1, M Gotthardt, A Barth
1Department of Nuclear Medicine of the Philipps-University of Marburg, Germany. tmbehr@mailer.uni-marburg.de
Abstract:
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.
Insights
Regulatory peptides target cancer cells via high-affinity receptors. Peptide-based radiopharmaceuticals offer new diagnostic and therapeutic nuclear oncology tools, with somatostatin analogs already approved for neuroendocrine tumor staging.
Area of Science:
- Nuclear Oncology
- Radiopharmaceutical Chemistry
- Molecular Imaging
Background:
- Regulatory peptides exhibit potent, receptor-mediated actions.
- Overexpression of peptide receptors in neoplasms presents novel molecular targets for cancer diagnosis and therapy.
- Peptide-based radiopharmaceuticals are emerging as key tools in oncology.
Purpose of the Study:
- To provide an overview of peptide-based radiopharmaceuticals for cancer diagnosis and therapy.
- To highlight currently available and clinically advanced peptide radiopharmaceuticals.
- To discuss the potential of novel peptide radioligands in nuclear oncology.
Main Methods:
- Review of clinical studies and regulatory approvals of peptide-based radiopharmaceuticals.
- Analysis of receptor binding characteristics and diagnostic accuracy of various peptide analogs.
- Exploration of ongoing research and development in peptide radioligand discovery.
Main Results:
- Somatostatin analogs, like 111In-DTPA-[D-Phe1]-octreotide, are approved for gastroenteropancreatic neuroendocrine tumor staging.
- Radiolabeled vasoactive intestinal peptide (VIP) visualizes gastrointestinal adenocarcinomas and some neuroendocrine tumors.
- Radiolabeled gastrin analogs target cholecystokinin B receptor-expressing cancers, including medullary thyroid cancer and small-cell lung cancer.
Conclusions:
- Radiolabeled regulatory peptides have significantly advanced nuclear oncology for diagnosis and potential radionuclide therapy.
- Somatostatin receptor scintigraphy is highly effective for neuroendocrine tumors but limited in other cancers.
- Ongoing development of diverse peptide radioligands promises expanded clinical applications in oncology.