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

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