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

Abstract

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.

Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

“…Herein we developed an innovative fluorescence contrast agent for lymphatic imaging in the optical transparency window (NIR‐IIb, >1500 nm). This imaging modality integrated the advantages of single‐photon emission computerized tomography (SPECT)/positron emission tomography (PET)/magnetic resonance imaging (MRI) and optical imaging, providing great penetration depth, high spatial resolution, and real‐time imaging speed.…”

Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer

“…However, for intraoperative imaging and tPDT, high absolute tumor accumulation of the ligands is essential for the sensitivity of fluorescence-guided surgery and the efficacy of tPDT, whereas uptake in other organs outside the surgical field is of less importance. PSMA-targeted tracers with a photosensitizer are designed to accumulate in PCa lesions and the fluorescence camera or light (normal or laparoscopic 680 nm laser) can be focused to the tumor site as well, meaning that PSMA-targeted intraoperative imaging and tPDT is highly precise 11 , 39 , 40 .…”

(Radio)Theranostic Patient Management in Oncology Exemplified by Neuroendocrine Neoplasms, Prostate Cancer, and Breast Cancer

“…The European Association of Nuclear Medicine published guidelines for radionuclide therapy with [ 177 Lu]Lu-labeled PSMA-ligand wherein PSMA-ligand/PET and [ 18 F]FDG/PET are recommended for the selection of patients that would benefit from the therapy [158]. PSMA-radioguided surgery in prostate cancer may further improve the treatment outcome [123,159,160].…”