title: Synthesis and biological characteristics of the four stereoisomers of 99mTc-N,N'-bis-(mercaptoacetyl)-2,3-diaminopropanoate.
abstract: To study the differences in biological behaviour between the four stereoisomers of 99mTc-CO2-DADS we synthesized both the L- and D-isomer of N,N'-bis-(benzoylmercaptoacetyl)-2,3-diaminopropanoic acid ethyl ester. The N2S2 ligands were labelled with 99mTc by the dithionite reduction method in alkaline medium to hydrolyze the ester function. Each isomer yielded two diastereomeric 99mTc-complexes, that were separated by RP-HPLC to finally obtain the four isomers of 99mTc-CO2-DADS. The biodistribution of the isomers was determined in mice and a baboon. The study in mice indicates that only the LB-isomer is responsible for the high liver uptake reported for (DL)-99mTc-CO2-DADS-B (Fritzberg et al. J. Nucl. Med. 23, 592-598, 1982). The rate of renal extraction and hepatobiliary excretion of the three other isomers is comparable to that of [131I]o-I-hippurate. Baboon renograms for the LA- and DA-isomers are similar to that of [123I]o-I-hippurate. The renogram of the DB-isomer resembles more the 99mTc-DTPA renogram, whereas the LB-isomer exhibits a 99mTc-DMSA-like renal build-up. It appears that minor configurational changes can drastically alter the renal handling of these bisamide bisthiol 99mTc-tracer agents.
authors.affiliation: Laboratory of Radiopharmaceutical Chemistry, Institute of Pharmaceutical Sciences, K. U. Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Bormans
authors.forename: B
authors.initials: B
authors.lastname: Cleynhens
authors.forename: D
authors.initials: D
authors.lastname: José
authors.forename: M
authors.initials: M
authors.lastname: Hoogmartens
authors.forename: M
authors.initials: M
authors.lastname: De Roo
authors.forename: A
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives*; D000818:Animals; D007465:Iodohippuric Acid; D008297:Male; D051379:Mice; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010215:Papio; D004369:Pentetic Acid; D011866:Radioisotope Renography; D013237:Stereoisomerism; D016284:Technetium Tc 99m Pentetate; D014018:Tissue Distribution; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D015609:Organotechnetium Compounds; C034974:technetium Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate; D015091:beta-Alanine; D007465:Iodohippuric Acid; D004369:Pentetic Acid; D000409:Alanine; D016284:Technetium Tc 99m Pentetate