Paula Demétrio de Souza França1, Sheryl Roberts2, Susanne Kossatz3, Navjot Guru4, Christian Mason5, Daniella Karassawa Zanoni6, Marcio Abrahão7, Heiko Schöder8, Ian Ganly9, Snehal G Patel10, Thomas Reiner11. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paulo, SP, Brazil. Electronic address: demetrip@mskcc.org. 2. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: roberts3@mskcc.org. 3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: s.kossatz@tum.de. 4. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: gurun@mskcc.org. 5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: masonc@mskcc.org. 6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7. Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paulo, SP, Brazil. 8. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: schoderh@mskcc.org. 9. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. Electronic address: ganlyi@mskcc.org. 10. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. Electronic address: patels@mskcc.org. 11. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: reinert@mskcc.org.
Abstract
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.
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]FDGPET 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 (humansquamous 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.
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