Radiosynthesis of 4-[(2-chloroethyl)(2-[11C]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- -glutamic acid was synthesised by reductive alkylation of 4-[(2-chloroethyl)amino]-phenoxycarbonyl- -glutamic acid using acetaldehyde. 4-[(2-chloroethyl)[11C](2-ethyl)amino]phenoxycarbonyl- -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- -glutamic acid using [11C]acetaldehyde. [11C]Acetaldehyde was prepared in 60% decay corrected radiochemical yield by oxidation of [11C]ethanol over heated copper oxide. The radiosynthesis of [11C]ethanol was re-examined and optimized. 4-[(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl- -glutamic acid was found to have affinity for carboxypeptidase G2; the Km and Vmax 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.