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 ([11C]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.
Eriks-Fluks
E
E
PET-center, Groningen University Hospital, The Netherlands.
Elsinga
P H
PH
Hendrikse
N H
NH
Franssen
E J
EJ
Vaalburg
W
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D002250:Carbon Radioisotopes; D002360:Carubicin / Q000737:chemistry; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D008745:Methylation; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D014055:Tomography, Emission-Computed / Q000379:methods
C111956:4-methoxydaunorubicin; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D002360:Carubicin; D003630:Daunorubicin