Prostate specific membrane antigen-radio guided surgery using Cerenkov luminescence imaging—utilization of a short-pass filter to reduce technical pitfalls

Intraoperative Cerenkov luminescence imaging (CLI) is a novel technique to assess surgical margins in patients undergoing nerve sparing radical prostatectomy (RP). Here, we analyze the efficacy of a 550-nm optical short-pass filter (OF) to improve its performance.In this prospective single-center feasibility study ten patients with prostate cancer (PC) were included between December 2019 and April 2020, including three patients without tracer injection as a control group. After preoperative injection of 68-Ga-prostate-specific membrane antigen (PSMA)-11 followed by RP, CLI of the excised prostate and the incised index lesion was performed to visualize the primary tumor lesion. We compared the findings on intraoperative CLI to postoperative histopathology. Furthermore, CLI-intensities determined as tumor to background ratio (TBR) and contrast to noise ratio (CNR) were measured.Histopathology proved positive surgical margins (PSM) in 3 patients with corresponding findings in CLI. After magnetic resonance imaging (MRI)-informed incision above the index lesion 2 out of 3 prostates demonstrated elevated CLI signals with histopathological confirmation of PC cells. The use of the OF enabled a significant reduction of the area of the regions of interest from a median of 1.80 to 0.15 cm2 (reduction by 85%, P=0.005) leading to increased specificity. Signals due to PSMs were not suppressed by the 550-nm OF. The median TBR was reduced from 3.33 to 2.10. In all three patients of the control group elevated CLI intensities were detected at locations with diathermal energy deposition during surgery. After application of the 550-nm OF these were almost totally suppressed with a TBR of 1.10. Measurements of Cerenkov luminescence intensity with the 550-nm OF showed a significant Pearson's correlation of 0.82 between PSM and the elevated TBR (P=0.003) and a significant Pearson's correlation of 0.66 between PSM and elevated CNR (P=0.04). Measurements without the OF did not correlate significantly.Intraoperative 68-Ga-PSMA CLI in PC is a tool that warrants further investigation to visualize PSM especially in intermediate and high-risk PC. Intraoperative CLI benefits from usage of a 550-nm OF to reduce false-positive signals.