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Purpose: Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using 68Ga-prostate-specific membrane antigen (68Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative 68Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff. Methods: Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq 68Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology. Results: By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer < 0.1 mm from the excision margin. Conclusion: Overall, the study showed that 68Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique. Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109. [ABSTRACT FROM AUTHOR]

Cerenkov luminescence imaging (CLI) was successfully implemented in the intraoperative context as a form of radioguided cancer surgery, showing promise in the detection of surgical margins during robot-assisted radical prostatectomy. The present study was designed to provide a quantitative description of the occupational radiation exposure of surgery and histopathology personnel from CLI-guided robot-assisted radical prostatectomy after the injection of 68 Ga-PSMA-11 in a single-injection PET/CT CLI protocol. Methods: Ten patients with preoperative 68 Ga-PSMA-11 administration and intraoperative CLI were included. Patient dose rate was measured before PET/CT ( n  = 10) and after PET/CT ( n  = 5) at a 1-m distance for 4 patient regions (head [A], right side [B], left side [C], and feet [D]). Electronic personal dosimetry (EPD) was used for intraoperative occupational exposure ( n  = 10). Measurements included the first surgical assistant and scrub nurse at the operating table and the CLI imager/surgeon at the robotic console and encompassed the whole duration of surgery and CLI image acquisition. An estimation of the exposure of histopathology personnel was performed by measuring prostate specimens ( n  = 8) with a germanium detector. Results: The measured dose rate value before PET/CT was 5.3 ± 0.9 (average ± SD) μSv/h. This value corresponds to a patient-specific dose rate constant for positions B and C of 0.047 μSv/h⋅MBq. The average dose rate value after PET/CT was 1.04 ± 1.00 μSv/h. The patient-specific dose rate constant values corresponding to regions A to D were 0.011, 0.026, 0.024, and 0.003 μSv/h⋅MBq, respectively. EPD readings revealed average personal equivalent doses of 9.0 ± 7.1, 3.3 ± 3.9, and 0.7 ± 0.7 μSv for the first surgical assistant, scrub nurse, and CLI imager/surgeon, respectively. The median germanium detector-measured activity of the prostate specimen was 2.96 kBq (interquartile range, 2.23-7.65 kBq). Conclusion: Single-injection 68 Ga-PSMA-11 PET/CT CLI procedures are associated with a reasonable occupational exposure level, if kept under 110 procedures per year. Excised prostate specimen radionuclide content was below the exemption level for 68 Ga. Dose rate-based calculations provide a robust estimation for EPD measurements., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intraoperatively during prostatectomy using 68 Ga-prostate-specific membrane antigen ( 68 Ga-PSMA-11). This study evaluated the accuracy of CLI compared with histopathology and, as an exploratory objective, investigated the characteristics of the identified chemiluminescence signal. Methods: After intravenous injection of a mean 68 Ga-PSMA-11 activity of 69 MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathologic comparison and scored for the likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in 3 radioactive and 3 nonradioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1 mm). In 6 hot spots, CLI correctly identified PSMs on histopathology, located at the apex and mid prostate. In all 15 patients, an increased signal at the prostate base was observed, without the presence of the primary tumor in this area in 8 patients. This chemiluminescence signal was also observed in nonradioactive prostate specimens, with a half-life of 48 ± 11 min. The chemiluminescence hampered the visual interpretation of 4 PSMs at the base. Conclusion: CLI was able to correctly identify margin status, including close margins, in 83% of the cases. The presence of a diathermy-induced chemiluminescent signal hampered image interpretation, especially at the base of the prostate. In the current form, CLI is most applicable to detect PSMs and close margins in the apex and mid prostate., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Our objective was to assess the feasibility and accuracy of Cerenkov luminescence imaging (CLI) for assessment of surgical margins intraoperatively during radical prostatectomy. Methods: A single-center feasibility study included 10 patients with high-risk primary prostate cancer (PC). 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT scans were performed followed by radical prostatectomy and intraoperative CLI of the excised prostate. In addition to imaging the intact prostate, in the first 2 patients the prostate gland was incised and imaged with CLI to visualize the primary tumor. We compared the tumor margin status on CLI to postoperative histopathology. Measured CLI intensities were determined as tumor-to-background ratio. Results: Tumor cells were successfully detected on the incised prostate CLI images as confirmed by histopathology. Three of 10 men had histopathologically positive surgical margins (PSMs), and 2 of 3 PSMs were accurately detected on CLI. Overall, 25 (72%) of 35 regions of interest proved to visualize a tumor signal according to standard histopathology. The median tumor radiance in these areas was 11,301 photons/s/cm 2 /sr (range, 3,328-25,428 photons/s/cm 2 /sr), and median tumor-to-background ratio was 4.2 (range, 2.1-11.6). False-positive signals were seen mainly at the prostate base, with PC cells overlaid by benign tissue. PSMA immunohistochemistry revealed strong PSMA staining of benign gland tissue, which impacts measured activities. Conclusion: This feasibility showed that 68 Ga-PSMA CLI is a new intraoperative imaging technique capable of imaging the entire specimen's surface to detect PC tissue at the resection margin. Further optimization of the CLI protocol, or the use of lower-energy imaging tracers such as 18 F-PSMA, is required to reduce false-positives. A larger study will be performed to assess diagnostic performance., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Currently, approximately 11-38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using 68 Ga-prostate-specific membrane antigen ( 68 Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative 68 Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff., Methods: Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq 68 Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology., Results: By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer < 0.1 mm from the excision margin., Conclusion: Overall, the study showed that 68 Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique., Trial Registration: NL8256 registered at www.trialregister.nl on 04/11/20109.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18 F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18 F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18 F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99m Tc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from 18 F-FDG. The cross-talk and 99m Tc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm 2 /sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 μSv per procedure. Conclusion: Intraoperative 18 F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)