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

Abstract

Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68 Ga-PSMA-11 is promising, although limited by low residual activity and artificial signals. Here, we aimed to assess the value of CLI and flexible autoradiography (FAR) with 18 F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18 F-PSMA-1007, and PET/CT was performed. After the animals had been killed, organs were excised and measured signals in CLI and FAR CLI were correlated with tracer activity concentrations (ACs) obtained from PET/CT. For clinical assessment, 7 high-risk PC patients underwent radical prostatectomy immediately after preoperative 18 F-PSMA PET/CT. Contrast-to-noise ratios (CNRs) were calculated for both imaging modalities in intact specimens and after incision above the index lesion. Results: In the heterotopic in vivo mouse model (n 5 5), CLI did not detect any lesion. FAR CLI detected a distinct signal in all mice, with a lowest AC of 7.25 kBq/mL (CNR, 5.48). After incision above the index lesion of the prostate specimen, no increased signal was observed at the cancer area in CLI. In contrast, using FAR CLI, a signal was detectable in 6 of 7 patients. The AC in the missed index lesion was 1.85 kBq/mL, resulting in a detection limit of at least 2.06 kBq/mL. Histopathology demonstrated 2 PRMs, neither of which was predicted by CLI or FAR CLI. Conclusion: 18 F-PSMA FAR CLI was superior to CLI in tracer-related signal detectability. PC was could be visualized in radical prostatectomy down to 2.06 kBq/mL. However, the detection of PRMs was limited. Direct anatomic correlation of FAR CLI is challenging because of the scintillator overlay.

Intraoperative Molecular Positron Emission Tomography Imaging for Intraoperative Assessment of Radical Prostatectomy Specimens

“…Overall, there were nine areas close to the surgical margin in addition to the PSM, all of which could be confirmed histopathologically. This very promising result is in contrast with other molecular imaging techniques such as Cerenkov luminescence imaging, where, on the one hand, artificial signals complicate the assessment and, on the other hand, the minimum activity was missed in our one stop protocol [6] , [7] . There was increased activity at the time of intraoperative imaging with 18 F-PSMA-1007 ( p = 0.01; Supplementary material , and Supplementary Fig.…”

Prostate-specific membrane antigen (PSMA) radioguided surgery in prostate cancer: An overview of current application and future perspectives

“…In this perspective, the use of an optical bypass filter or the implementation of CLI with 18F-PSMA compounds might further improve the detection rate of positive surgical margins, increasing the signal detectability of more superficial lesions. Fluorine-18 has, indeed, a significantly shorter positron range in tissues than 68 Ga (0.54 vs. 2.83 mm) [23].…”