Urokinase-Type Plasminogen Activator Receptor (uPAR) PET/MRI of Prostate Cancer for Noninvasive Evaluation of Aggressiveness: Comparison with Gleason Score in a Prospective Phase 2 Clinical Trial

Abstract

The aim of this study was to evaluate the correlation between uptake of the positron emission tomography (PET) ligand 68 Ga-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) and Gleason score in patients undergoing prostate biopsy. Materials & methods: Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase II trial. A combined uPAR PET, multiparametric magnetic resonance imaging (mpMRI) was performed and standardized uptake value (SUV) from primary tumor, as delineated by mpMRI, was measured by two independent readers. Correlation between SUV and Gleason score obtained by biopsy was assessed. Results: A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between SUV max and Gleason score (Spearman's rho= 0.55; p=0.003). Receiver operating characteristics analysis showed an area under the curve (AUC) of 0.88 (95%CI: 0.67-1.00) in discriminating Gleason score ≥3+4 from ≤3+3. A cutoff for tumor SUVmax could be established with a sensitivity of 96% (79-99%) and specificity of 75% (30-95%) in detecting Gleason Scores ≥3+4. For discriminating Gleason score ≥ 4+3 vs. ≤ 3+4, a cutoff could be established for detecting Gleason score ≥ 4+3 with a sensitivity of 93% (69-99%) and specificity of 62% (36-82%). Conclusion: SUV measurements from uPAR PET in primary tumors as delineated by mpMRI showed a significant correlation with Gleason score, and tumor SUV max was able to discriminate between low-risk and intermediate risk Gleason score profiles with high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for non-invasive evaluation of PCa, which may in the future potentially reduce the need for repeated biopsies, e.g. in active surveillance.

uPAR PET/CT for Prognostication and Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing Radium-223 Therapy: A Prospective Phase II Study

“…68 Ga-NOTA-AE105 PET has been validated in a phase I study including prostate cancer patients, where uptake of the ligand corresponded to uPAR expression in excised tissue [13]. Additionally, in a recent phase II PET/MRI trial in patients with prostate cancer, we found a clear correlation between tumor uptake of the ligand and Gleason score, which confirmed the ligand as an imaging marker of prostate cancer aggressiveness [14].…”

Potential Targets Other Than PSMA for Prostate Cancer Theranostics: A Systematic Review

“…We included 47 studies that investigated the use of radioligands that target six different receptors of tumor cells for imaging or therapy of PCa patients. The most studied receptors in PCa were gastrin-releasing peptide receptors ( n = 23 studies) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ] and the androgen receptor ( n = 11 studies) [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], followed by somatostatin receptors ( n = 6 studies) [ 45 , 46 , 47 , 48 , 49 , 50 ], the urokinase plasminogen activator surface receptor ( n = 4 studies) [ 51 , 52 , 53 , 54 ], the fibroblast activation protein ( n = 2 studies) [ 55 , 56 ] and integrin receptors ( n = 1 study) [ 57 ]. As only phase I and II studies were available, the risk of bias and uncertainty were not assessed.…”

Side-by-Side Comparison of uPAR-Targeting Optical Imaging Antibodies and Antibody Fragments for Fluorescence-Guided Surgery of Solid Tumors

“…Furthermore, immunohistochemical studies have revealed absent to low levels of uPAR expression in healthy homeostatic tissue whereas at the interface between tumor and healthy tissue, uPAR is highly overexpressed on both tumor and tumor-associated stromal cells [8][9][10][11][12]. Such a pattern is ideal for imaging and, not surprisingly, a PET tracer is currently undergoing extensive clinical trials in order to image "cancer aggressiveness" and subsequently aid in tailoring treatment options to disease biology [13].…”