Synthesis and biological evaluation of [¹¹C]AZ12504948; a novel tracer for imaging of glucokinase in pancreas and liver.

Glucokinase (GK) is potentially a target for imaging of islets of Langerhans. Here we report the radiosynthesis and preclinical evaluation of the GK activator, [(11)C]AZ12504948, for in vivo imaging of GK. [(11)C]AZ12504948 was synthesized by O-methylation of the precursor, AZ125555620, using carbon-11 methyl iodide ([(11)C]CH₃I). Preclinical evaluation was performed by autoradiography (ARG) of human tissues and PET/CT studies in pig and non-human primate. [(11)C]AZ12504948 was produced in reproducible good radiochemical yield in 28-30 min. Radiochemical purity of the formulated product was >98% for up to 2 h with specific radioactivities 855 ± 209 GBq/μmol (n=8). The preclinical evaluation showed some specificity for GK in liver, but not in pancreas. [(11)C]AZ12504948 images GK in liver, but the low specificity impedes the visualization of GK in pancreas. Improved target specificity is required for further progress using PET probes based on this class of GK activators.