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

Abstract

Objective: To assess the feasibility and accuracy of Cerenkov Luminescence Imaging (CLI) for assessment of surgical margins intraoperatively during radical prostatectomy (RPE). Methods:A single centre feasibility study included 10 patients with high-risk primary prostate cancer (PC). 68 Ga-PSMA PET/CT scans were performed followed by RPE and intraoperative CLI of the excised prostate. In addition to imaging the intact prostate, in the first two patients the prostate gland was incised and imaged with CLI to visualise the primary tumour. We compared the tumour margin status on CLI to postoperative histopathology. Measured CLI intensities were determined as tumour to background ratio (TBR).Results: Tumour cells were successfully detected on the incised prostate CLI images as confirmed by histopathology. 3 of 10 men had histopathological positive surgical margins (PSMs), and 2 of 3 PSMs were accurately detected on CLI. Overall, 25 (72%) out of 35 regions of interest (ROIs) proved to visualize a tumour signal according to standard histopathology. The median tumour radiance in these areas was 11301 photons/s/cm 2 /sr (range 3328 -25428 photons/s/cm 2 /sr) and median TBR 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 (PSMA-IHC) revealed strong PSMA staining of benign gland tissue, which impacts measured activities.Conclusions: 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 optimisation of the CLI protocol, or the use of lower-energetic imaging tracers such as 18 F-PSMA, are required to reduce false positives. A larger study will be performed to assess diagnostic performance.

Prostaatspecifiek membraanantigeengestuurde chirurgie voor prostaatkanker

“…Weer een andere techniek om peroperatief de chirurgische snijranden tijdens radicale prostatectomie te beoordelen, is Cerenkov luminescence imaging [29,30]. Cerenkov-luminescentie is een zwak licht dat wordt uitgezonden door een radioactieve verbinding [31]. Het zogenaamde Cerenkov-licht ontstaat op het moment dat een elektrisch geladen deeltje zich door een diëlektrisch medium verplaatst met een snelheid groter dan de fasesnelheid van licht in dat medium [32].…”

“…Naast een hoge sensitiviteit en specificiteit van PSMA voor de detectie van prostaatkankerlaesies middels PET, blijkt gallium-68 ( 68 Ga)-PSMA uitermate geschikt te zijn voor Cerenkov-luminescentie door de relatief hoge Cerenkovopbrengt. 68 Ga-PSMA Cerenkov luminescence imaging is een beeldvormende techniek die het Cerenkovlicht, dat wordt uitgezonden door 68 Ga-PSMA, detecteert met een zeer gevoelige camera (Lightpoint Medical Ltd) [31]. Deze techniek zou geschikt zijn voor patiënten met een PSMA-avide primaire tumor die in aanmerking komen voor radicale prostatectomie.…”

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

“…In contrast to PET, CLI is unable to detect photons emitted by deeper located tissues or tumors (25,26). Intraoperative imaging with CLI is promising since it allows to evaluate the entire surface of the prostate instead of only specific IFS slices (27,28). Besides the good agreement between CLI and histopathology, there is also evidence of false-positive signals mainly at the bladder neck (27).…”

“…Intraoperative imaging with CLI is promising since it allows to evaluate the entire surface of the prostate instead of only specific IFS slices (27,28). Besides the good agreement between CLI and histopathology, there is also evidence of false-positive signals mainly at the bladder neck (27). Artificial signals caused by longer wavelengths can make intraoperative assessment more difficult and even lead to unnecessary resections of healthy tissue.…”

In-vitro Study for Cerenkov Luminescence Imaging Application in Hepatic Metastasectomy

“…If before surgery the patient has received an intravenous injection of a PET radiopharmaceutical with high uptake in the tumor, CLI of the resected specimen, by providing bidimensional images of the Cerenkov photons at the tissue surface, can tell if surgical margins are negative (absence of signal in the image) or positive (presence of signal). A few clinical studies have already demonstrated the feasibility of CLI for intraoperative specimen analysis, in neurosurgery [3], in breast conserving surgery [4] and in radical prostatectomy [5,6].…”