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
• positron emission tomography
• precision medicine
• prostate cancer
• head and neck cancer
• neuroendocrine tumors
• urokinase-type plasminogen activator receptor

Article highlights

• The urokinase-type plasminogen activator receptor (uPAR) has emerged as a novel biomarker of tumor aggressiveness and metastatic potential.

• Various efforts have been made to synthesize radiopharmaceuticals, such as [⁶⁸Ga]Ga-NOTA-AE105 and [⁶⁴Cu]Cu-DOTA-AE105, for in vivo imaging of uPAR expression in cancer using positron emission tomography (PET).

• Both uPAR-targeted radiopharmaceuticals showed favorable biodistribution and dosimetry and were effective in detecting primary tumors and metastases.

• In head and neck cancer, uPAR-PET showed potential for patient stratification prior to curative radiotherapy, as increased tracer uptake correlated with poor relapse-free survival.

• For prostate cancer surveillance, uPAR-PET showed promising results by accurately identifying Gleason scores equal to or greater than 4 + 3.

• uPAR-PET demonstrated the ability to detect both low and high grade neuroendocrine neoplasia and correlated with patient outcomes in terms of progression-free survival and overall survival.

• Despite promising initial findings, further studies are needed to validate uPAR-PET and define the most appropriate clinical applications for this new imaging modality.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

R. Camedda and L Filippi designed the review study; R. Danieli and V. Frantellizzi performed the literature research and data extraction; R. Camedda, L. Filippi, R. Danieli and G. D. Vincentis wrote the paper; G. D. Vincentis and L Filippi supervised the paper.

Additional information

Funding

The paper was not funded.