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A novel radiochemical approach to 1‐(2'‐deoxy‐2'‐[ 18 F]fluoro‐β‐ d ‐arabinofuranosyl)cytosine ( 18 F‐FAC)
Author(s) -
Meyer JanPhilip,
Probst Katrin C.,
Trist Iuni M. L.,
McGuigan Christopher,
Westwell Andrew D.
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3233
Subject(s) - radiosynthesis , chemistry , radiochemistry , cytidine , cytosine , in vivo , nucleoside , specific activity , reactivity (psychology) , positron emission tomography , stereochemistry , nuclear medicine , organic chemistry , enzyme , dna , biochemistry , medicine , microbiology and biotechnology , biology , alternative medicine , pathology
18 F‐FAC (1‐(2'‐deoxy‐2'‐[ 18 F]fluoro‐β‐D‐arabinofuranosyl)‐cytosine) is an important 2'‐fluoro‐nucleoside‐based positron emission tomography (PET) tracer that has been used for in vivo prediction of response to the widely used cancer chemotherapy drug gemcitabine. Previously reported synthetic routes to 18 F‐FAC have relied on early introduction of the 18 F radiolabel prior to attachment to protected cytosine base. Considering the 18 F radiochemical half‐life (110 min) and the technical challenges of multi‐step syntheses on PET radiochemistry modular systems, late‐stage radiofluorination is preferred for reproducible and reliable radiosynthesis with in vivo applications. Herein, we report the first late‐stage radiosynthesis of 18 F‐FAC. Cytidine derivatives with leaving groups at the 2'‐position are particularly prone to undergo anhydro side‐product formation upon heating because of their electron density at the 2‐carbonyl pyrimidone oxygen. Our rationally developed fluorination precursor showed an improved reactivity‐to‐stability ratio at elevated temperatures. 18 F‐FAC was obtained in radiochemical yields of 4.3–5.5% (n = 8, decay‐corrected from end of bombardment), with purities ≥98% and specific activities ≥63 GBq/µmol. The synthesis time was 168 min.