Positron emission computed tomography targeting urokinase plasminogen activator receptor (uPAR) in cancer: a systematic review

Abstract

Introduction: To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator receptor in oncology.

Methods: A literature search was conducted in PubMed, Web of Science and Scopus databases up to June 2023. The results were presented according to the PRISMA guidelines. The quality of the studies was assessed using the Critical Appraisal Skill Program checklist.

Results: Seven papers were selected for final analysis, involving 266 patients with solid tumors who underwent PET with uPAR-ligands. Thematic areas identified include feasibility studies (n = 2) on the safety, pharmacokinetics, and dosimetry of uPAR-targeting radiopharmaceuticals; uPAR-directed imaging in head and neck cancer (n = 2); uPAR PET in prostate cancer (n = 2); and the investigation of uPAR in neuroendocrine neoplasms (n = 1). Six of the seven studies used the radiopharmaceutical [⁶⁸Ga]Ga-NOTA-AE105 while one study used [⁶⁴Cu]Cu-DOTA-AE105. The studies showed protocol homogeneity, with static PET imaging at 20 minutes. The quality assessment revealed limitations such as small cohorts and the fact that all studies were performed by a single research group.

Conclusions: uPAR-PET appears to be a promising imaging tool in well-selected oncological settings, but it needs to be validated by multicentre collaboration.

Keywords: Molecular imaging; head and neck cancer; neuroendocrine tumors; positron emission tomography; precision medicine; prostate cancer; urokinase-type plasminogen activator receptor.