PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

SIMPLE SUMMARY: Positron emission tomography/computed tomography (PET/CT) has an increasingly relevant role in the management of oncological patients. It consists of the administration of a radioactive molecule (tracer) which localizes in tumour cells due to specific cellular features (e.g., a receptor expressed by a specific cell population). PET/CT has a variety of applications in oncology, including staging, therapeutic response assessment and restaging in various types of tumours through the administration of different tracers. Among them, prostate-specific membrane antigen (PSMA) radioligands are a relatively novel compound widely employed in prostate cancer diagnostics and therapy. Besides their prostate cancer applications, PSMA radioligands have been shown to be a promising instrument to evaluate the stage and the aggressiveness in several types of cancer, since they allow us to study tumour neoangiogenesis. This review provides an overview of the applications of PSMA radioligand PET/CT in various types of tumours other than prostate cancer. ABSTRACT: Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.