SYNTHESIS OF NCA C-11 LABELED CLOZAPINE AND ITS MAJOR METABOLITE CLOZAPINE-N-OXIDE AND COMPARISON OF THEIR BIODISTRIBUTION IN MICE

N.c.a. [C-11]clozapine, hyl-1-piperazinyl)-5H-dibenzo[b,e]-1,4-diazepi ne], 1, an atypical neuroleptic was synthesized by N-methylation of th e desmethyl compound norclozapine, 3, using [C-11]methyl iodide or [C- 11]methyl triflate for comparison. Subsequent oxidation of 1 with m-ch loroperoxybenzoic acid yielded clozapine-N-oxide, 2, the major metabol ite of 1. Purification of both radiolabelled products was carried out using a combined semi-preparative HPLC/solid phase extraction procedur e. In preparative scale runs overall radiochemical yields for 1 and 2 were 70 and 65%, respectively. The radiochemical purities of both comp ounds exceeded 98% and the specific activities were in the range of 99 -130 GBq/mu mol (2.5-3.5 Ci/mu mol). Biodistribution of 1 and 2 has be en studied in NMRI mice. 10 min p.i. clozapine shows a 24-fold higher brain uptake than its major metabolite. At 60 min p.i., however, the c erebral uptake of both compounds is almost identical.