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

Autor:	Tang W; Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA., Kuruvilla SA; Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA., Galitovskiy V; Cancer Center and Research Institute, University of California Irvine, California 92697, USA., Pan ML; Preclinical Imaging, Department of Radiological Sciences, University of California Irvine, California 92697, USA., Grando SA; Department of Dermatology, University of California Irvine, California 92697, USA ; Cancer Center and Research Institute, University of California Irvine, California 92697, USA., Mukherjee J; 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.
Jazyk:	angličtina
Zdroj:	American journal of nuclear medicine and molecular imaging [Am J Nucl Med Mol Imaging] 2014 Jun 07; Vol. 4 (4), pp. 324-32. Date of Electronic Publication: 2014 Jun 07 (Print Publication: 2014).
Abstrakt:	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.
Databáze:	MEDLINE
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