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Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[18F]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.

SUBMITTER: Demetrio de Souza Franca P 

PROVIDER: S-EPMC7253343 | biostudies-literature | 2020 May - Jun

REPOSITORIES: biostudies-literature

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Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[<sup>18</sup>F]fluoro-d-glucose positron emission tomography in oral cancer imaging.

Demétrio de Souza França Paula P   Roberts Sheryl S   Kossatz Susanne S   Guru Navjot N   Mason Christian C   Zanoni Daniella Karassawa DK   Abrahão Marcio M   Schöder Heiko H   Ganly Ian I   Patel Snehal G SG   Reiner Thomas T  

Nuclear medicine and biology 20200123


<h4>Objectives</h4>The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[<sup>18</sup>F]fluoro-d-glucose ([<sup>18</sup>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, [<sup>18</sup>F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinic  ...[more]

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