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.
Robot-assisted laparoscopic surgery is becoming an established technique for prostatectomy and is increasingly being explored for other types of cancer. Linking intraoperative imaging techniques, such as fluorescence guidance, with the three-dimensional insights provided by preoperative imaging remains a challenge. Navigation technologies may provide a solution, especially when directly linked to both the robotic setup and the fluorescence laparoscope. We evaluated the feasibility of such a setup. Preoperative single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) or intraoperative freehand SPECT (fhSPECT) scans were used to navigate an optically tracked robot-integrated fluorescence laparoscope via an augmented reality overlay in the laparoscopic video feed. The navigation accuracy was evaluated in soft tissue phantoms, followed by studies in a human-like torso phantom. Navigation accuracies found for SPECT/CT-based navigation were 2.25 mm (coronal) and 2.08 mm (sagittal). For fhSPECT-based navigation, these were 1.92 mm (coronal) and 2.83 mm (sagittal). All errors remained below the <1-cm detection limit for fluorescence imaging, allowing refinement of the navigation process using fluorescence findings. The phantom experiments performed suggest that SPECT-based navigation of the robot-integrated fluorescence laparoscope is feasible and may aid fluorescence-guided surgery procedures.