Intraoperative 68Ga-PSMA Cerenkov Luminescence Imaging for Surgical Margins in Radical Prostatectomy: A Feasibility Study

Abstract

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). ⁶⁸Ga-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/cm²/sr (range, 3,328-25,428 photons/s/cm²/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 ⁶⁸Ga-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 ¹⁸F-PSMA, is required to reduce false-positives. A larger study will be performed to assess diagnostic performance.

Keywords: Cerenkov luminescence imaging; margin assessment; prostate cancer; radical prostatectomy; radioguided surgery.

FIGURE 1.

Gray-scale photographs overlaid with Cerenkov signals for incised prostate gland specimen of patients 1 (A) and 2 (B). In each image, ROIs are encircled. Incision is marked with dotted line. Light blue ROI (area of empty specimen tray) and dark blue ROI (area of normal prostate tissue) were used as empty background and tissue background, respectively. Green ROI (lesion 1) and pink ROI (lesion 2) show increased signal; histopathologic analysis confirmed cancer tissue in these areas. Orange ROI in B shows increased signal from area without cancer cells.

FIGURE 2.

Gray-scale photographs overlaid with Cerenkov signal for patients 1 (A), 5 (B), and 6 (C), with PSMs. Elevated signal (arrow) from tumor can be seen in A and B. Elevated signal without histopathologic tumor cell correlation is displayed in C (arrow). Immunohistochemistry showed PSMA expression of benign tissue in this region.

FIGURE 3.

PSMA immunohistochemistry correlation of prostate base, running from patient 1 (A) to patient 8 (H). Green crosses = PSMA immunohistochemistry expression of benign gland tissue; red crosses = PSMA immunohistochemistry expression of carcinoma; green and red striped crosses = PSMA immunohistochemistry expression of benign gland tissue and carcinoma. Crosses display analyzed side (left or right prostate base). Additionally, larger crosses symbolize higher amount of tumor cells. Yellow stars display increased Cerenkov intensity in this area.