Radiosynthesis of 4-[(2-chloroethyl)(2-[C]ethyl)amino]-phenoxycarbonyl- -glutamic acid a half mustard prodrug as a potential probe for imaging antibody- and gene-directed enzyme prodrug therapy with positron emission tomography

The potential antibody directed prodrug therapy half-mustard prodrug 4-(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was synthesised by reductive alkylation of 4-(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using acetaldehyde. 4-(2-chloroethyl)(11)C](2-ethyl)amino]phenoxycarbonyl-L-glutamic acid was synthesized with 18-22% decay corrected radiochemical yield in 45 min from EOB by reductive alkylation of 4-(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using (11)C]acetaldehyde. (11)C]Acetaldehyde was prepared in 60% decay corrected radiochemical yield by oxidation of (11)C]ethanol over heated copper oxide. The radiosynthesis of (11)C]ethanol was re-examined and optimized. 4-(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was found to have affinity for carboxypeptidase G2; the K(m) and V(max) were 99.4-115.9 microM (n=3) and 3.6-5.0 microM/min, respectively, at a carboxypeptidase G2 concentration of 0.0247 U/ml.