Targeting histone deacetylase in lung cancer for early diagnosis: F-18-FAHA PET/CT imaging of NNK-treated A/J mice model

Elevated levels of histone deacetylases (HDACs) have been indicated in the development of some cancers. HDAC has been imaged using F-18-FAHA and may serve as a marker to study epigenetics. We report evaluation of F-18-FAHA as a probe in the early diagnosis of lung cancer using F-18-FAHA PET/CT studies of A/J mice treated with NNK. F-18-FAHA radiosynthesis was carried out in specific activity of similar to 2 Ci/mu mol. 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 mu Ci i.v. F-18-FAHA and then scanned in Inveon PET/CT under anesthesia using 2.0% isoflurane. Midbrain, cerebellum and brainstem uptake of F-18-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 F-18-FAHA was observed in the control mice lungs while significant F-18-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 F-18-FAHA in the NNK mice with tumor/nontumor >6.0. Our preliminary imaging studies with A/J mice lung cancer model suggest F-18-FAHA PET may allow the study of epigenetic mechanisms involved in NNK-induced tumorigenesis in the lungs.