Peptide Receptor Radionuclide Therapy: Looking Back, Looking Forward.

Peptide receptor radionuclide therapy (PRRT) is a highly effective anti-cancer treatment modality for patients with non-resectable, metastasized neuroendocrine tumors (NETs). During PRRT, specific receptors that are overexpressed on the cancer cells are targeted with a peptide labeled with a DNA-damaging radionuclide. Even though PRRT is a powerful treatment for metastasized NET patients, the majority still cannot be cured at this stage of the disease. Hence, many investigators focus on improving the therapeutic efficacy of this therapy. Improving PRRT can, for example, be achieved by using other radionuclides with different physical properties, by combining PRRT with radiosensitizing agents or by radiolabeling peptides with different characteristics. However, due to lack of extensive knowledge of radiobiological responses of cancer cells to PRRT, biological parameters that influence absorbed dose or that might even elicit insensitivity to therapy remain elusive and the context in which these improvements will be successful warrants further investigation. In this review, we will discuss the development of PRRT, its clinical merits in current treatment and future perspectives. We will highlight different radionuclides and their benefits and pitfalls, as well as different peptide-conjugates that hold these radionuclides. We will zoom in on the latest developments regarding combinatorial treatments and how investigators from different disciplines such as dosimetry and radiobiology are now joining forces to improve PRRT for NETs.