¹⁸F-FAHA PET for imaging histone deacetylase in lung cancer

Objectives Histone deacetylase has been imaged using ¹⁸F-FAHA and may serve as a marker to study epigenetics. We report evaluation of ¹⁸F-FAHA as a probe in the early diagnosis of lung cancer using longitudinal MicroPET/MicroCT ¹⁸F-FAHA studies of A/J mice treated with NNK.

Methods ¹⁸F-FAHA radiosynthesis was carried out in specific activity of ~2 Ci/μmol as reported (Mukhopadhyay 2006). A/J mice acquired from Jackson Labs were divided into 2 groups: 1. Controls for CT/PET; 2. NNK treatment group for CT/PET. Group 2 animals received NNK (100 mg/kg, ip, weekly for 4 wks). Mice were injected 50-100 μCi i.v. ¹⁸F-FAHA and then scanned in Inveon MicroPET/CT under anesthesia using 2.0% isoflurane. Ex vivo PET/CT scans of lungs were also obtained on some mice after the in vivo scans. Sections (5 to 10μm thick) of the isolated lungs were prepared for H&E staining and autoradiographic studies.

Results MicroCT revealed presence of lung nodules in 8 mo old mice while control mice were free of tumors. Little uptake of ¹⁸F-FAHA was in the control mice lungs while significant amount of ¹⁸F-FAHA was seen in the lungs of NNK treated mice. Quantitative analysis of the extent and amount of ¹⁸F-FAHA binding provided in vivo lung tumor/nontumor = >2.0. Studies of control A/J mice lungs showed little binding of ¹⁸F-FAHA, uniformly distributed. 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 ¹⁸F-FAHA in the NNK mice while no tumors were detected in the control mice.

Conclusions Our preliminary imaging studies with A/J mice lung cancer model suggests ¹⁸F-FAHA PET may allow the study of epigenetic mechanisms involved in NNK induced tumorigenesis in the lungs. Further studies on the ability of ¹⁸F-FAHA to detect the lung tumors earlier are underway