Related resources
Full-text held externally
Search for item elsewhere
University researcher(s)
Academic department(s)
Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with (18)F-FAHA
Yeh, H H; Tian, M; Hinz, R; Young, D; Shavrin, A; Mukhapadhyay, U; Flores, L G; Balatoni, J; Soghomonyan, S; Jeong, H J; Pal, A; Uthamanthil, R; Jackson, J N; Nishii, R; Mizuma, H; Onoe, H; Kagawa, S; Higashi, T; Fukumitsu, N; Alauddin, M; Tong, W; Herholz, K; Gelovani, J G
Neuroimage. 2013;64:630-9.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
Abstract
Epigenetic modifications mediated by histone deacetylases (HDACs) play important roles in the mechanisms of different neurologic diseases and HDAC inhibitors (HDACIs) have shown promise in therapy. However, pharmacodynamic profiles of many HDACIs in the brain remain largely unknown due to the lack of validated methods for noninvasive imaging of HDAC expression-activity. In this study, dynamic PET/CT imaging was performed in 4 rhesus macaques using [(18)F]FAHA, a novel HDAC substrate, and [(18)F]fluoroacetate, the major radio-metabolite of [(18)F]FAHA, and fused with corresponding MR images of the brain. Quantification of [(18)F]FAHA accumulation in the brain was performed using a customized dual-tracer pharmacokinetic model. Immunohistochemical analyses of brain tissue revealed the heterogeneity of expression of individual HDACs in different brain structures and cell types and confirmed that PET/CT/MRI with [(18)F]FAHA reflects the level of expression-activity of HDAC class IIa enzymes. Furthermore, PET/CT/MRI with [(18)F]FAHA enabled non-invasive, quantitative assessment of pharmacodynamics of HDAC inhibitor SAHA in the brain.
Bibliographic metadata
- Related website http://www.ncbi.nlm.nih.gov/pubmed/22995777
- Yeh, Hsin-Hsien Tian, Mei Hinz, Rainer Young, Daniel Shavrin, Alexander Mukhapadhyay, Uday Flores, Leo G Balatoni, Julius Soghomonyan, Suren Jeong, Hwan J Pal, Ashutosh Uthamanthil, Rajesh Jackson, James N Nishii, Ryuichi Mizuma, Hiroshi Onoe, Hirotaka Kagawa, Shinya Higashi, Tatsuya Fukumitsu, Nobuyoshi Alauddin, Mian Tong, William Herholz, Karl Gelovani, Juri G RC2 DA028912/DA/NIDA NIH HHS/United States United States NeuroImage Neuroimage. 2013 Jan 1;64:630-9. doi: 10.1016/j.neuroimage.2012.09.019. Epub 2012 Sep 17.