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

Abstract

Background: 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. Methods: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.Results: 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 cm 2 (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.Conclusions: 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.

State of the Art in Prostate-specific Membrane Antigen–targeted Surgery—A Systematic Review

“…The ex vivo evaluation of 68 Ga-PSMA-11 with the DROP-IN beta probe correctly identified positive surgical margins in 40% (seven patients) [15] . Ex vivo Cerenkov imaging of 68 Ga-PSMA-11 yielded 60–83% (37 patients) agreement with histopathology [16] , [20] , [21] , [22] . Eder et al [36] and Aras et al [34] describe the visibility of the fluorescent component of the tracer (in and ex vivo, respectively) but did not quantify their results.…”

“…We included 29 reports on PSMA-targeted surgery ( Fig. 2 ), of which eight were prospective studies [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , 12 retrospective analyses [4] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , and nine case reports [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] Generally, a small number of patients were included: in eight of 29 (28%) reports ≥20 patients were included, of which two (retrospective) studies included >100 patients (7%). The remaining 72% of studies can be considered small-scale pilots or first-in-man reports ( Fig.…”

“…For the most commonly used tracers ( 99m Tc-PSMA-I&S and 111 In-PSMA-I&T), the mean injection time to surgery was around 24 h (range 16–28 h), with a median injected activity varying between 541 and 638 MBq and between 140 and 150 MBq, respectively. Studies used 68 Ga-PSMA-11 injected between 76 and 127 MBq [16] , [20] . A detailed description of the timing and injected activity of all tracers can be found in Supplementary Table 2 .…”

Radiolabeled PSMA Inhibitors

“…Radiation dose to workers limits the use to 62 procedures/year of this technique, but improvements towards a lower occupational radiation dose are feasible. Alternative imaging technologies focusing on beta-radiation emission, e.g., Cerenkov luminescence imaging using [ 68 Ga]Ga-PSMA-11 are currently under early clinical investigation [ 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”

18F-PSMA Cerenkov Luminescence and Flexible Autoradiography Imaging in a Prostate Cancer Mouse Model and First Results of a Radical Prostatectomy Feasibility Study in Men

“…However, so far, only feasibility studies have been described, and larger multicenter randomized trials are pending. In addition, clinical application without intraoperative tracer injection is challenged by the short half-life of 68 Ga and the time required for prostate removal (18)(19)(20). 18 F-PSMA CLI would easily overcome this restriction with respect to the half-life.…”