PSMA-targeting agents for radio- and fluorescence-guided prostate cancer surgery

Despite recent improvements in imaging and therapy, prostate cancer (PCa) still causes substantial morbidity and mortality. In surgical treatment, incomplete resection of PCa and understaging of possible undetected metastases may lead to disease recurrence and consequently poor patient outcome. To increase the chance of accurate staging and subsequently complete removal of all cancerous tissue, prostate specific membrane antigen (PSMA) targeting agents may provide the surgeon an aid for the intraoperative detection and resection of PCa lesions. Two modalities suitable for this purpose are radionuclide detection, which allows sensitive intraoperative localization of tumor lesions with a gamma probe, and fluorescence imaging, allowing tumor visualization and delineation. Next to fluorescence, use of photosensitizers may enable intraoperative targeted photodynamic therapy to eradicate remaining tumor lesions. Since radiodetection and optical imaging techniques each have their own strengths and weaknesses, a combination of both modalities could be of additional value. Here, we provide an overview of recent preclinical and clinical advances in PSMA-targeted radio- and fluorescence-guided surgery of PCa.