ENZYMATIC-SYNTHESIS OF [4-METHOXY-C-11]DAUNORUBICIN FOR FUNCTIONAL IMAGING OF P-GLYCOPROTEIN WITH PET

One of the mechanisms for multidrug resistance (MDR) of tumors is an o verexpression of the P-glycoprotein (P-gp). The cytostatic agent dauno rubicin was labeled with carbon-11 to probe P-gp with PET. An enzymati c route for the conversion of carminomycin to [4-methoxy-C-11]daunorub icin ([4-methoxy-C-11]DNR) was investigated, since attempts failed to prepare daunorubicin chemically using [C-11]methyl iodide. In the enzy matic synthesis methylation was accomplished by S-adenosyl-L-[methyl-C -11]methionine ([C-11]SAM), which was synthesized from L-[methoxy-C-11 ]methionine. This methylation is catalyzed by carminomycin-4-O-methylt ransferase (CMT). The overall radiochemical yield of [4-methoxy-C-11]D NR is 1% (EOB), with a total synthesis time of 75 min. In conclusion, [4-methoxy-C-11]DNR can be successfully prepared from carminomycin and [C-11]SAM using enzymes. (C) 1998 Elsevier Science Ltd. All rights re served.