Abstract
OBJECTIVES: The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) PET is often complicated by physiological uptake in normal tissues of the head and neck region, especially after surgery or radiotherapy. However, irrespective of low positive predictive values, [(18)F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinical use of a targeted poly (ADP-ribose) polymerase1 (PARP1) binding PET tracer, fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor ([(18)F]PARPi), as a potential alternative with greater specificity. METHODS: Using an orthotopic xenograft mouse model injected with either FaDu or Cal 27 (human squamous cell carcinoma cell lines) we performed PET/CT scans with the 2 tracers and compared the results. Gamma counts and autoradiography were also assessed and correlated with histology. RESULTS: The average retained activity of [(18)F]PARPi across cell lines in tumor-bearing tongues was 0.9 ± 0.3%ID/g, 4.1 times higher than in control (0.2 ± 0.04%ID/g). Autoradiography and histology confirmed that the activity arose almost exclusively from the tumor areas, with a signal/normal tissue around a ratio of 42.9 ± 21.4. In vivo, [(18)F]PARPi-PET allowed delineation of tumor from healthy tissue (p < .005), whereas [(18)F]FDG failed to do so (p = .209). CONCLUSIONS AND IMPLICATIONS FOR PATIENT CARE: We demonstrate that [(18)F]PARPi is more specific to tongue tumor tissue than [(18)F]FDG. [(18)F]PARPi PET allows for the straightforward delineation of oral cancer in mouse models, suggesting that clinical translation could result in improved imaging of head and neck cancer when compared to [(18)F]FDG.