title: Radiosynthesis of 4-[(2-chloroethyl)(2-[(11)C]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 microM (n=3) and 3.6-5.0 microM/min, respectively, at a carboxypeptidase G2 concentration of 0.0247 U/ml.
authors.affiliation: Hammersmith Imanet, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Nazreen
authors.initials: N
authors.lastname: Malik
authors.forename: S K Sajinder K
authors.initials: SK
authors.lastname: Luthra
authors.forename: Phil
authors.initials: P
authors.lastname: Burke
authors.forename: P M Patrica M
authors.initials: PM
authors.lastname: Price
authors.forename: E O Eric O
authors.initials: EO
authors.lastname: Aboagye
authors.forename: John
authors.initials: J
authors.lastname: Latigo
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Frank
authors.initials: F
authors.lastname: Brady
mesh_terms: D000079:Acetaldehyde; D000816:Aniline Mustard / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D019275:Radiopharmaceuticals; D013379:Substrate Specificity; D014055:Tomography, Emission-Computed; D011623:gamma-Glutamyl Hydrolase
chemical_list: C096843:(4-(N,N-bis(2-chloroethyl)amino)phenoxycarbonyl)glutamic acid; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D000816:Aniline Mustard; D011623:gamma-Glutamyl Hydrolase; D000079:Acetaldehyde