title: (99m)Tc complexes with activated ester functions; ligands comprising a 3,4-diamino-benzoate backbone.
abstract: Preformed (99m)Tc chelates with an activated ester function are useful for the gentle labeling of proteins (precomplexation route). In this context, new heterobifunctional ligands derived from 2,3,5,6-tetrafluorophenyl (TFP) 3,4-diamino-benzoates (OC1, OC3, OC4) were synthesized. Their corresponding (99m)Tc-complexation and protein-conjugation characteristics were elucidated and compared with the results previously reported using 2,3,5,6-tetrafluorophenyl N-(S-benzoylthioacetyl)glycylglycyl-p-aminobenzoate (OC2). The reaction temperatures and the reaction time markedly influenced complexation yields. Compared with OC2, the (99m)Tc-chelate formation with OC1 and OC4 was more effective, showing radiochemical yields of 60% and 70% within 20 min, respectively. Owing to steric hindrance, the complexation of OC3, however, did not exceed 10%. No-carrier-added (99m)Tc complexes were conjugated at pH 10 with the anti-EGF-receptor monoclonal antibody MAb425, resulting in labeling yields of 14% for (99m)Tc-OC1 and 7% for (99m)Tc-OC4 after incubating for 20 min at 30 degrees C. Increasing the temperature to 40 degrees C improved these results by 14% and 3%, respectively. As compared with (99m)Tc-OC2, which provides the chelating substituent at the 4-phenyl position only, the application of 3,4-phenyl substituents proved less appropriate for protein conjugation. However, the 3,4-diaminobenzoate backbone may be attractive for an alternative design of novel (99m)Tc N2S2 or N3S complexes, because they show excellent complexation characteristics.
authors.affiliation: Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Osmar Calderon
authors.initials: OC
authors.lastname: Sanchez
authors.forename: Ashour
authors.initials: A
authors.lastname: Mohammed
authors.forename: Claudia
authors.initials: C
authors.lastname: Bauer
authors.forename: Markus
authors.initials: M
authors.lastname: Wolf
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.forename: Raoul
authors.initials: R
authors.lastname: Mocelo
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry; D062365:Aminobenzoates / Q000138:chemical synthesis*; D000911:Antibodies, Monoclonal; D002614:Chelating Agents / Q000138:chemical synthesis; D066246:ErbB Receptors / Q000276:immunology; D004952:Esters / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism*; D062366:para-Aminobenzoates
chemical_list: C487559:2,3,5,6-tetrafluorophenyl N-(S-benzoylthioacetyl)glycylglycyl- p-aminobenzoate; D062365:Aminobenzoates; D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D004952:Esters; D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D062366:para-Aminobenzoates; C041192:3,4-diaminobenzoic acid; D066246:ErbB Receptors; D010129:4-Aminobenzoic Acid