Radiosynthesis of 4-[(2-chloroethyl)(2-[11C]ethyl)amino]-phenoxycarbonyl-L-glutamic acid a half mustard prodrug as a potential probe for imaging antibody- and gene-directed enzyme prodrug therapy with positron emission tomography

Abstract 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 μM ( n =3) and 3.6–5.0 μM/min, respectively, at a carboxypeptidase G2 concentration of 0.0247 U/ml.