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. Academic Article uri icon

Overview

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.

publication date

  • January 23, 2020

Research

keywords

  • Enzyme Inhibitors
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Mouth Neoplasms
  • Poly (ADP-Ribose) Polymerase-1
  • Positron-Emission Tomography

Identity

PubMed Central ID

  • PMC7253343

Scopus Document Identifier

  • 85080062394

Digital Object Identifier (DOI)

  • 10.1016/j.nucmedbio.2020.01.004

PubMed ID

  • 32135475

Additional Document Info

volume

  • 84-85