Hiroshi Shimadzu

Synthesis of 3,4‐dihydro‐5‐[11C]methoxy‐1(2H)‐isoquinolinone as a potential tracer for poly(ADP‐ribose) synthetase

Synthesis of 3,4-dihydro-5-[ 11 C]methoxy-1(2H)-isoquinolinone ([ 11 C]MIQO), a potent poly (ADP-ribose) synthetase inhibitor, was devised in order to evaluate whether it is possible to image excessive activation of poly(ADP-ribose) synthetase (PARS) by positron emission tomography. [ 11 C]MIQO was prepared by O-[C]methylation of 3,4-dihydro-5-hydroxy-1(2H)-isoquinolinone, obtained by a Schmidt reaction with 4-hydroxy-1-indanone, sodium azide and trichloroacetic acid, with [ 11 C]methyl triflate. Total synthesis time from EOB was 35 minutes. The radiochemical yield based on [ 11 C]carbon dioxide was 31±8% (n=8; decay corrected). The final product had a specific activity of 76 GBq/μmol at EOS, and the radiochemical purity of [ 11 C]MIQO was over 99%.