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Pharmaceuticals 2018, 11(4), 136; https://doi.org/10.3390/ph11040136

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

1
Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
2
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
*
Authors to whom correspondence should be addressed.
Received: 31 October 2018 / Revised: 6 December 2018 / Accepted: 11 December 2018 / Published: 13 December 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 and macrophages. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases. 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 molar activity. Preliminary PET imaging with [11C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation. View Full-Text
Keywords: neuroinflammation; microglia; carbon-11; radiochemistry; positron emission tomography neuroinflammation; microglia; carbon-11; radiochemistry; positron emission tomography
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Tanzey, S.S.; Shao, X.; Stauff, J.; Arteaga, J.; Sherman, P.; Scott, P.J.H.; Mossine, A.V. Synthesis and Initial In Vivo Evaluation of [11C]AZ683—A Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R). Pharmaceuticals 2018, 11, 136.

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