ArticleNuclear medicine and biology2011
The synthesis and evaluation of N1-(4-(2-[18F]-fluoroethyl)phenyl)-N8-hydroxyoctanediamide ([18F]-FESAHA), a PET radiotracer designed for the delineation of histone deacetylase expression in cancer.
Article in Nuclear medicine and biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- High-Contrast PET Imaging with [Journal of medicinal chemistry · 2023Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- HDAC Inhibitors: Innovative Strategies for Their Design and Applications.Molecules (Basel, Switzerland) · 2022Review
- Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction.Nature communications · 2022Article
- Design, synthesis, biochemical evaluation, radiolabeling and in vivo imaging with high affinity class-IIa histone deacetylase inhibitor for molecular imaging and targeted therapy.European journal of medicinal chemistry · 2022Article
- Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2018Review
- Novel Histone Deacetylase Class IIa Selective Substrate Radiotracers for PET Imaging of Epigenetic Regulation in the Brain.PloS one · 2015Article
- Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors.ACS chemical neuroscience · 2014Article
- Rational development of radiopharmaceuticals for HIV-1.Nuclear medicine and biology · 2014Review
- Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model.American journal of nuclear medicine and molecular imaging · 2014Article
- Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain.Bioorganic & medicinal chemistry letters · 2013Article
- Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with ¹⁸F-FAHA.NeuroImage · 2013Article
- Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.Molecular imagingReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
introductionGiven the significant utility of suberoylanilide hydroxamic acid (SAHA) in chemotherapeutic protocols, a PET tracer that mimics the histone deacetylase (HDAC) inhibition of SAHA could be a valuable tool in the diagnosis, treatment planning and treatment monitoring of cancer. Here, we describe the synthesis, characterization and evaluation of N(1)-(4-(2-[(18)F]-fluoroethyl)phenyl)-N(8)-hydroxyoctanediamide ([(18)F]-FESAHA), a PET tracer designed for the delineation of HDAC expression in cancer.
methodsFESAHA was synthesized and biologically characterized in vivo and in vitro. [(18)F]-FESAHA was then synthesized in high radiochemical purity, and the logP and serum stability of the radiotracer were determined. In vitro cellular uptake experiments and acute biodistribution and small-animal PET studies were performed with [(18)F]-FESAHA in mice bearing LNCaP xenografts.
results[(18)F]-FESAHA was synthesized in high radiochemical purity via an innovative one-pot procedure. Enzymatic inhibition assays illustrated that FESAHA is a potent HDAC inhibitor, with IC(50) values from 3 nM to 1.7 μM against the 11 HDAC subtypes. Cell proliferation experiments revealed that the cytostatic properties of FESAHA very closely resemble those of SAHA in both LNCaP cells and PC-3 cells. Acute biodistribution and PET imaging experiments revealed tumor uptake of [(18)F]-FESAHA and substantially higher values in the small intestine, kidneys, liver and bone.
conclusionThe significant non-tumor background uptake of [(18)F]-FESAHA presents a substantial obstacle to the use of the radiotracer as an HDAC expression imaging agent. The study at hand, however, does present a number of lessons critical to both the synthesis of hydroxamic acid containing PET radiotracers and imaging agents aimed at delineating HDAC expression.
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