Performance evaluation of Cerenkov Luminescence Imaging: A comparison of ^sup 68^Gawith ^sup 18^F

Objectives: Cerenkov Luminescence Imaging (CLI) is an emerging technology which has potential for intraoperative tumour margin assessment, for example in prostate cancer surgery. CLI involves optical imaging of Cerenkov photons, which are emitted when a charged particle (from a beta-emitting isotope) travels faster than the phase velocity of light within tissue. Currently, CLI has been performed in breast cancer using the general tracer, 18Fluorine-fluorodeoxyglucose (18F-FDG). 68Gallium prostate-specific membrane antigen (68Ga-PSMA) is highly specific for prostate cancer imaging and should theoretically have a higher signal intensity but lower resolution compared to 18F due to the higher β-energy. Therefore, the aim of this study was to investigate the optical properties of 68Ga and 18F for CLI. Methods: CLI images using 18F and 68Gawere acquired using the LightPath system (Lightpoint Medical, Chesham, UK), with an exposure time of 120s, 2x2 binning and 300s, 8x8 binning, in both protocols no optical filter was used. In all experiments 3 Eppendorf tubes containing 1mL clear aqueous solution with 40, 10 and 2.5kBq were used. These clinically relevant concentrations where chosen based upon SUVmax measurements in 35 primary prostate cancer patients who underwent a 68Ga-PSMA PET 45 minutes after intravenous injection of approximately 100MBq. The Eppendorf tubes were shielded from ambient light during the acquisition. Images were acquired every 20 minutes for up to 4 hours in total, to evaluate the light yield, linearity and camera sensitivity. The spatial resolution (Full-Width Half-Maximum, FWHM) was determined using a 1mm slit in a non-transparent plastic block, which was filled with 0.035mL of 47kBq activity. All experiments were repeated under subsequently stacked 1mm slices of chicken breast fillet (CBF). A square 15mL homogeneity phantom was imaged with the size of the field of view (FOV 6x6cm) to assess field homogeneity. Results: For both radioisotopes, an excellent linear relationship between the amount of radioactivity and detected light yield (radiance) was observed (R2 =0.99), which persisted with the addition of 1mm CBF. 68Ga showed approximately 22 times more detectable Cerenkov light per disintegration compared to 18F, in both situations. Furthermore, the radiance half-life was 115.1min for 18F and 69.3min for 68Ga, consistent with the expected values of the both activity half-lives, respectively 109.8 and 67.8min. The detectable level with 300