In vivo PET imaging of histone deacetylases by 18F- suberoylanilide hydroxamic acid (18F-SAHA) Academic Article uri icon

Overview

MeSH Major

  • Fluorine Radioisotopes
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids

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 likewise show that HDAC inhibitor target binding efficacy can be quantitated within 24 h of administration. 1a thus represents the first (18)F-positron emission tomography (PET) HDAC imaging agent, which also exhibits low nanomolar potency and is pharmacologically analogous to a clinically relevant HDAC inhibitor.

publication date

  • August 11, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3150598

Digital Object Identifier (DOI)

  • 10.1021/jm200620f

PubMed ID

  • 21721525

Additional Document Info

start page

  • 5576

end page

  • 82

volume

  • 54

number

  • 15