Enzymatic synthesis of [4-methoxy-11C]daunorubicin for functional imaging of P-glycoprotein with PET.

One of the mechanisms for multidrug resistance (MDR) of tumors is an overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin was labeled with carbon-11 to probe P-gp with PET. An enzymatic route for the conversion of carminomycin to [4-methoxy-C-11]daunorubicin ([4-methoxy-C-11]DNR) was investigated, since attempts failed to prepare daunorubicin chemically using [C-11]methyl iodide. In the enzymatic 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-methyltransferase (CMT). The overall radiochemical yield of [4-methoxy-C-11]DNR 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 reserved.