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.

Keywords: PET; PSMA; nuclear medicine; radioligand; theragnostics; therapy.

Figure 1

Summary of study selection process for the review.

Figure 2

A 57-years old man with diagnosis of prostate adenocarcinoma previously treated through external beam radiation therapy in 2019 (Gleason score 4 + 4) came to our attention in December 2021 for biochemical recurrence (PSA value: 0.91 ng/mL) and underwent restaging ¹⁸F-PSMA-1007 PET/CT. PET/CT scan was performed 90 min after 270 MBq ¹⁸F-PSMA-1007 administration. PET/CT images showed focal uptake in the prostate gland right lobe, attributable to prostate cancer relapse. Furthermore, in the head and neck sections ((A) fused PET/CT axial, (B) fused PET/CT coronal, (C) low-dose CT axial, (D) low-dose CT coronal), an area of abnormal and intense ¹⁸F-PSMA-1007 uptake was observed in a thyroid nodule located in the right lobe. After routine diagnostic work up, the patient underwent total thyroidectomy without lymph-node dissection, and histologic examination was consistent with the diagnosis of tall cell variant papillary thyroid cancer.

Figure 3

A 64-years old man with diagnosis of prostate adenocarcinoma previously treated through robot-assisted radical prostatectomy and pelvic lymph-node dissection in 2016 (pT2apN0c; Gleason score 4 + 3) came to our attention in February 2022 for biochemical recurrence (PSA value: 0.64 ng/mL) and underwent ¹⁸F-PSMA-1007 PET/CT. PET/CT scan was performed 90 min after 250 MBq ¹⁸F-PSMA-1007 administration. PET/CT images did not show any sign of suspect local recurrence nor distant metastases distinctly attributable to prostate cancer. Nevertheless, in the upper abdomen sections ((A) fused PET/CT axial, (B) fused PET/CT coronal, (C) fused PET/CT sagittal, (D) low-dose CT axial, (E) low-dose CT coronal; (F): low-dose CT sagittal), an area of abnormal and intense ¹⁸F-PSMA-1007 uptake was observed in an exophitic lesion located at the lower pole of the left kidney (white arrow). After routine diagnostic work up, the patient was submitted to total nephrectomy and histologic examination was consistent with the diagnosis of ccRCC.