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

Sean S Tanzey; Xia Shao; Jenelle Stauff; Janna Arteaga; Phillip Sherman; Peter J H Scott; Andrew V Mossine

doi:10.3390/ph11040136

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

Pharmaceuticals (Basel). 2018 Dec 13;11(4):136. doi: 10.3390/ph11040136.

Authors

Sean S Tanzey¹, Xia Shao², Jenelle Stauff³, Janna Arteaga⁴, Phillip Sherman⁵, Peter J H Scott^{6

7}, Andrew V Mossine⁸

Affiliations

¹ Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. tanzeys@umich.edu.
² Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. xshao@umich.edu.
³ Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. jrstauff@umich.edu.
⁴ Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. jannaa@umich.edu.
⁵ Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. psherman@umich.edu.
⁶ Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. pjhscott@umich.edu.
⁷ Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. pjhscott@umich.edu.
⁸ Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. avmossine@gmail.com.

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 (K_i = 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.

Keywords: carbon-11; microglia; neuroinflammation; positron emission tomography; radiochemistry.

Abstract

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