Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography in oral cancer imaging Journal Article

   

Authors:	Demétrio De Souza França, P.; Roberts, S.; Kossatz, S.; Guru, N.; Mason, C.; Zanoni, D. K.; Abrahão, M.; Schöder, H.; Ganly, I.; Patel, S. G.; Reiner, T.
Article Title:	Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography in oral cancer imaging
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. © 2020 Elsevier Inc.
Keywords:	controlled study; protein expression; unclassified drug; squamous cell carcinoma; nonhuman; animal cell; mouse; animal tissue; animal experiment; animal model; drug specificity; histology; feasibility study; drug accumulation; fluorodeoxyglucose f 18; tracer; mouth cancer; autoradiography; pet/ct; oral cancer; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; radiological parameters; oncological parameters; tumor delineation; article; positron emission tomography-computed tomography; [18f]parpi; [18f]fdg; 2-deoxy-2-[18f]fluoro-d-glucose; fluorine-18 labeled poly (adp-ribose) polymerase1 inhibitor; poly(adenosine diphosphate ribose)polymerase 1 inhibitor f 18; gamma count
Journal Title:	Nuclear Medicine and Biology
Volume:	84-85
ISSN:	0969-8051
Publisher:	Elsevier Science Inc.
Date Published:	2020-05-01
Start Page:	80
End Page:	87
Language:	English
DOI:	10.1016/j.nucmedbio.2020.01.004
PROVIDER:	scopus
PUBMED:	32135475
PMCID:	PMC7253343
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85080062394&doi=10.1016%2fj.nucmedbio.2020.01.004&partnerID=40&md5=a39ee3c0fa7eb01995e27939bf510ed3
Notes:	Article -- Export Date: 1 April 2020 -- Source: Scopus

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