Synthesis and Evaluation of 2-[18 F]Fluoroethyltriazolesuberohydroxamine Acid for Histone Deacetylase in a Tumor Model as a Positron Emission Tomography Radiotracer

Cancer Biotherapy & Radiopharmaceuticals
In Sun KimHwan-Jeong Jeong

Abstract

Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18F]fluoroethyltriazolesuberohydroxamine acid ([18F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats. [18F]FETSAHA was produced in less than 2 h with 31.2% ± 4.6% (n = 6) decay-corrected yields and specific activity of 21.4 ± 9.1 GBq/μmol (n = 6) at end of synthesis. [18F]FETSAHA showed significant radioactivity accumulation in tumors with rapid blood clearance and both gastrointestinal track and renal excretion. Tumor-to-blood and tumor-to-muscle uptake ratios in the RR1022 tumor bearing rat model were 1.21 and 1.83 and 2.75 and 2.76 at 30 and 60 min, respectively. An inhibition study of [18F]FETSAHA in the presence of excess amount of suberanilohydroximic acid (SAHA) revealed receptor specific activity accumulation. [18F]FETSAHA has favorable in vivo tumor imaging properties and may be useful for noninvasive evalua...Continue Reading

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Citations

Jun 23, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Chu TangJie Tian

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Methods Mentioned

BETA
acetylation
xenografts
xenograft

Software Mentioned

PMOD

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