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

J Nucl Med. 2023 Apr;64(4):598-604. doi: 10.2967/jnumed.122.264670. Epub 2022 Nov 10.

Abstract

Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68Ga-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 18F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18F-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 18F-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), 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: 18F-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.

Keywords: Cerenkov luminescence imaging; flexible autoradiography; margin assessment; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Feasibility Studies
  • Gallium Radioisotopes
  • Humans
  • Luminescence
  • Male
  • Mice
  • Positron Emission Tomography Computed Tomography / methods
  • Positron-Emission Tomography / methods
  • Prostate* / diagnostic imaging
  • Prostate* / pathology
  • Prostate* / surgery
  • Prostatectomy / methods
  • Prostatic Neoplasms* / diagnostic imaging
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / surgery

Substances

  • Gallium Radioisotopes