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

Synthesis of 3,4-dihydro-5-[C-11]methoxy-1(2H)-isoquinolinone ([C-11]MIQO), a potent poly (ADP-ribose) synthetase inhibitor, was devised in order to e valuate whether it is possible to image excessive activation of poly(ADP-ri bose) synthetase (PARS) by positron emission tomography. [C-11]MIQO was pre pared by O-[C-11]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 [C-11]methyl triflate. Total synthesis time fro m EOB was 35 minutes. The radiochemical yield based on [C-11]carbon dioxide was 31+/-8% (n=8; decay corrected). The final product had a specific activ ity of 76 GBq/mu mol at EOS, and the radiochemical purity of [C-11]MIQO was over 99%.