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

oleh: Sean S. Tanzey, Xia Shao, Jenelle Stauff, Janna Arteaga, Phillip Sherman, Peter J. H. Scott, Andrew V. Mossine

Format: Article
Diterbitkan: MDPI AG 2018-12-01

Deskripsi

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><sub>i</sub></i> = 8 nM; IC<sub>50</sub> = 6 nM) and &gt;250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [<sup>11</sup>C]AZ683 and initial evaluation of its use in CSF1R PET. [<sup>11</sup>C]AZ683 was synthesized by <sup>11</sup>C-methylation of the desmethyl precursor with [<sup>11</sup>C]MeOTf in 3.0% non-corrected activity yield (based upon [<sup>11</sup>C]MeOTf), &gt;99% radiochemical purity and high molar activity. Preliminary PET imaging with [<sup>11</sup>C]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.