Intraoperative specimen assessment in prostate cancer surgery using Cerenkov luminescence imaging

Intraoperative margin assessment during prostate cancer (PCa) surgery might reduce the number of positive surgical margins (PSM). Cerenkov Luminescence Imaging (CLI) based on optical imaging of PET radiopharmaceuticals is suitable for this purpose. Previous CLI research has been conducted with 18Fluorine, however, 68Gallium has more favorable CLI properties and can be coupled to a prostate cancer specific tracer: the prostate-specific membrane antigen (68Ga-PSMA). Light yield, resolution and camera sensitivity of 68Ga and 18F for CLI were investigated in a pre-clinical setting. CLI images were acquired using the LightPath system, with an exposure time of 120s, 2×2 binning and 300s, 8×8 binning. Three Eppendorf tubes (1mL) with different radioactivity concentrations (2.5, 10 and 40kBq/mL) of 18F and 68Ga were imaged. For both isotopes, an excellent linear relationship between the radioactivity concentration and detected light yield was observed (R2=0.99). 68Ga showed 22× more light yield compared to 18F, thus enabled lower detectable radioactivity concentration levels (1.2 vs. 23.7kBq/mL). Based on these promising results, a prospective feasibility study for intraoperative prostate cancer specimen CLI measurements with 68Ga-PSMA was designed and the first patients were enrolled in this study. The prostate was imaged ex vivo with the LightPath system ~70 minutes after injection of ~100MBq 68Ga-PSMA. Hotspots on the CLI images were marked for comparison with histopathology and corresponded to a PSM, defined as tumor on ink. In the first patients, CLI correctly identified all patients with a PSM. The encouraging preliminary results motivated for continuation of this trial.