(99m)Tc complexes with activated ester functions; ligands comprising a 3,4-diamino-benzoate backbone.
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.
Sanchez
Osmar Calderon
OC
Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg, Germany.
Mohammed
Ashour
A
Bauer
Claudia
C
Wolf
Markus
M
Wängler
Björn
B
Mier
Walter
W
Haberkorn
Uwe
U
Mocelo
Raoul
R
Eisenhut
Michael
M
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
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