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Synthesis and Initial In Vivo Evaluation of [11C]AZ683 – a Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

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Submitted:

31 October 2018

Posted:

02 November 2018

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Abstract
Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases and, in this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high specific activity. Preliminary PET imaging with [11C]AZ683 revealed no brain uptake in rodents and nonhuman primates suggesting that [11C]AZ683 is a poor candidate for imaging neuroinflammation, but that it could still be useful for peripheral imaging of inflammation.
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Subject: Chemistry and Materials Science  -   Medicinal Chemistry
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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