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

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

  • J Med Chem. 2011 Aug 11;54(15):5576-82. doi: 10.1021/jm200620f.
J Adam Hendricks 1 Edmund J Keliher Brett Marinelli Thomas Reiner Ralph Weissleder Ralph Mazitschek
Affiliations

Affiliation

  • 1 Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Massachusetts 02114, United States.
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-159045
    99.90%, HDACi