Document Detail


Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with ¹⁸F-FAHA.
MedLine Citation:
PMID:  22995777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hsin-Hsien Yeh; Mei Tian; Rainer Hinz; Daniel Young; Alexander Shavrin; Uday Mukhapadhyay; Leo G Flores; Julius Balatoni; Suren Soghomonyan; Hwan J Jeong; Ashutosh Pal; Rajesh Uthamanthil; James N Jackson; Ryuichi Nishii; Hiroshi Mizuma; Hirotaka Onoe; Shinya Kagawa; Tatsuya Higashi; Nobuyoshi Fukumitsu; Mian Alauddin; William Tong; Karl Herholz; Juri G Gelovani
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-17
Journal Detail:
Title:  NeuroImage     Volume:  64     ISSN:  1095-9572     ISO Abbreviation:  Neuroimage     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-26     Completed Date:  2013-06-04     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Anilides
Animals
Brain / enzymology*,  metabolism*
Epigenesis, Genetic / physiology
Female
Fluorine Radioisotopes / diagnostic use,  pharmacokinetics*
Gene Expression Regulation, Enzymologic / physiology
Histone Deacetylases / metabolism*
Macaca mulatta
Magnetic Resonance Imaging / methods*
Male
Molecular Imaging / methods*
Positron-Emission Tomography / methods*
Subtraction Technique
Grant Support
ID/Acronym/Agency:
1RC2DA028912/DA/NIDA NIH HHS; RC2 DA028912/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/6-(fluoroacetamido)-1-hexanoicanilide; 0/Anilides; 0/Fluorine Radioisotopes; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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