Synthesis and Initial In Vivo Evaluation of [<sup>11</sup>C]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

Pharmaceuticals (Dec 2018)

Synthesis and Initial In Vivo Evaluation of [<sup>11</sup>C]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

Affiliations

Sean S. Tanzey: Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Xia Shao: Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Jenelle Stauff: Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Janna Arteaga: Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Phillip Sherman: Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Peter J. H. Scott: Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Andrew V. Mossine: Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA

DOI: https://doi.org/10.3390/ph11040136
Journal volume & issue: Vol. 11, no. 4
p. 136

Abstract

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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.

Published in Pharmaceuticals

ISSN: 1424-8247 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceuticals/

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