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-¹¹C]daunorubicin ([4-methoxy-¹¹C]DNR) was investigated, since attempts failed to prepare daunorubicin chemically using [¹¹C]methyl iodide. In the enzymatic synthesis methylation was accomplished by S-adenosyl-L-[methyl- ¹¹C]methionine ([¹¹]SAM), which was synthesized from L-[methyl- ¹¹C]methionine. This methylation is catalyzed by carminomycin-4-O- methyltransferase (CMT). The overall radiochemical yield of [4- methoxy.¹¹C]DNR is 1% (EOB), with a total synthesis time of 75 min. In conclusion, [4-methoxy-¹¹C]DNR can be successfully prepared from carminomycin and [¹¹C]SAM using enzymes.