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

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.

PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score

“…The existing scores were introduced mainly to assess treatment response, but the advent of new specific radiopharmaceuticals (e.g., PSMA-ligands compounds) underlined the need for a standardized method for imaging interpretation too. In this setting, PSMA showed to be the most promising tracer for PCa with high sensitivity and specificity, even if its role in different pathological conditions has been reported [ 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. In this scenario, several criteria for interpreting PSMA-ligand PET were proposed.…”

Nuclear Medicine and Cancer Theragnostics: Basic Concepts

“…In another study, the use of 68 Ga-PSMA-11 brain PET/CT for the evaluation of recurrent glioma also showed increased PSMA uptake, and the absence of normal brain uptake resulted in much better visualization of glioma lesions [74]. Interestingly, when compared to conventional 18 F-FDG PET, PSMA-targeting radiopharmaceuticals have the advantage of lower uptake in the normal brain [75]. However, despite the efficacy of PSMA-based molecules as diagnostic tools, there are still no clinical studies to evaluate their potential therapeutic role in glioma patients.…”

Role of Ga68 Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography in Prostate Cancer Imaging

“…In the most recent years, there is an increased interest in the potential application of PSMA ligand imaging in nonprostate neoplasms, with encouraging results in renal cell carcinoma and gliomas, while less favorable evidence for thyroid and gastroenteric neoplasms exists. 108 Few data are available about the mechanism of PSMA expression by immune cells. It is possible that neovascularization also plays a role in this scenario, as well as an increased availability of PSMA ligands to the site of inflammation/infection due to an increase in regional blood flow/vascular permeability.…”