Radiolabeled PSMA Inhibitors

SIMPLE SUMMARY: Prostate cancer remains one of the leading causes of cancer death in men worldwide. Despite the recent success in the development and clinical application of radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) for diagnosis and endoradiotherapy of prostate cancer, more research is ongoing to further investigate and improve patient care and quality of life. Herein, an overview of novel developments and applications for small molecule and low-molecular weight radiolabeled PSMA inhibitors with an outlook to clinical translation is given. ABSTRACT: PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin α(v)β(3). An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.