Objectives: The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]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, [¹⁸F]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 ([¹⁸F]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 [¹⁸F]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, [¹⁸F]PARPi-PET allowed delineation of tumor from healthy tissue (p < .005), whereas [¹⁸F]FDG failed to do so (p = .209).

Conclusions and implications for patient care: We demonstrate that [¹⁸F]PARPi is more specific to tongue tumor tissue than [¹⁸F]FDG. [¹⁸F]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 [¹⁸F]FDG.