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.
Sean S Tanzey  1 ,  Xia Shao  2 ,  Jenelle Stauff  3 ,  Janna Arteaga  4 ,  Phillip Sherman  5 ,  Peter J H Scott  6  7 ,  Andrew V Mossine  8
Affiliations
  • 1. Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 2. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 3. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 4. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 5. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 6. Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 7. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 8. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
PMID: 30551596 DOI: 10.3390/ph11040136
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.

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