In vivo PET imaging of histone deacetylases by 18F-suberoylanilide hydroxamic acid (18F-SAHA).

ABSTRACT: Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression and cell state by deacetylation of both histone and non-histone proteins. A variety of HDAC inhibitors (HDACi) have already undergone clinical testing in cancer. Real-time in vivo imaging of HDACs and their inhibition would be invaluable; however, the development of appropriate imaging agents has remained a major challenge. Here, we describe the development and evaluation of (18)F-suberoylanilide hydroxamic acid ((18)F-SAHA 1a), a close analogue of the most clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We demonstrate that 1a has near identical biochemical activity profiles to that of SAHA and report findings from pharmacokinetic studies. Using a murine ovarian cancer model, we lik

SUBMITTER: Hendricks JA 

PROVIDER: S-EPMC3150598 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature