DEVELOPMENT OF BIFUNCTIONAL CHELATES WITH ALIPHATIC AMINE DONORS FOR THE COMPLEXATION WITH THE {M(CO)_3}~+ CORE (M = Re, ~99mTc)

摘要

The labeling of small bioactive peptides with ~99mTc has been a major goal in nuclear medicine.13 Our goal is to develop a ~99mTc tracer for renal imaging. There are two strategies for ~99mTc radiopharmaceutical design: integrated or bifunctional approaches. The integrated approach involves direct labeling with incorporation of ~99mTc into the structure of peptide. In contrast, the bifunctional approach allows retention of the receptor binding affinity by connecting a radionuclide to the targeting molecule through bifunctional chelate (BFC). Careful selection of BFC, in which one functionality is covalently attached to the targeting molecules while the other stabilizes the nuclide, is required to assure stability and sufficient labeling with high yield. We studied two polyamines, N,N-bis(2-aminoethyl)glycine (DTGH) and diethylenetriamine-N-malonic acid (DTMH2), that coordinate tridentately to the {M(CO)3}~+ core (M = Re, ~99mTc). These ligands have the diethylenetriamine backbone and one or two auxiliary acetate donors. The combination of the terminal amine group and an acetate group allows insertion of the chelate at any position along the peptide sequence, or alternatively allows facile conjugation of biomolecules through formation of amide links.