title: Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model.
abstract: Elevated levels of histone deacetylases (HDACs) have been indicated in the development of some cancers. HDAC has been imaged using (18)F-FAHA and may serve as a marker to study epigenetics. We report evaluation of (18)F-FAHA as a probe in the early diagnosis of lung cancer using (18)F-FAHA PET/CT studies of A/J mice treated with NNK. (18)F-FAHA radiosynthesis was carried out in specific activity of ~2 Ci/μmol. A/J mice were divided into 2 groups: 1. Controls; 2. NNK treatment group with NNK (100 mg/kg, ip, weekly for 4 wks). Mice were injected 100-200 μCi i.v. (18)F-FAHA and then scanned in Inveon PET/CT under anesthesia using 2.0% isoflurane. Midbrain, cerebellum and brainstem uptake of (18)F-FAHA was displaced by the known HDAC inhibitor, suberanilohydroxamic acid (SAHA) with less than 10% activity remaining. CT revealed presence of lung nodules in 8 to 10-month old NNK mice while control mice were free of tumors. Little uptake of (18)F-FAHA was observed in the control mice lungs while significant (18)F-FAHA uptake occurred in the lungs of NNK-treated mice with tumor/nontumor >2.0. Ex vivo scans of the excised NNK and control mice lungs confirmed presence of extensive amounts of lung nodules seen by CT and confirmed by (18)F-FAHA in the NNK mice with tumor/nontumor >6.0. Our preliminary imaging studies with A/J mice lung cancer model suggest (18)F-FAHA PET may allow the study of epigenetic mechanisms involved in NNK-induced tumorigenesis in the lungs.
authors: Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA.
authors: Wayland
authors: W
authors: Tang
authors: Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA.
authors: Sharon A
authors: SA
authors: Kuruvilla
authors: Cancer Center and Research Institute, University of California Irvine, California 92697, USA.
authors: Valentin
authors: V
authors: Galitovskiy
authors: Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA.
authors: Min-Liang
authors: ML
authors: Pan
authors: Department of Dermatology, University of California Irvine, California 92697, USA ; Cancer Center and Research Institute, University of California Irvine, California 92697, USA.
authors: Sergei A
authors: SA
authors: Grando
authors: Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA ; Cancer Center and Research Institute, University of California Irvine, California 92697, USA.
authors: Jogeshwar
authors: J
authors: Mukherjee
keywords: 18F-FAHA; 18F-FDG; 18F-Nifene; A/J mice; Lung cancer; NNK; PET/CT; histone deacetylase