Non-ionic bulky Gd(III) DTPA-bisamide complexes as potential contrast agents for magnetic resonance imaging

A series of new diethylene triamine pentaacetic acid (DTPA)-bisamide chelates containing bulky alkyl and aryl side chains have been prepared and characterized. Nuclear magnetic relaxation dispersion profiles were measured for the neutral gadolinium [Gd(III)] DTPA-bisamide complexes in water solution, and their chemical exchange times (tau(m)) were found to be in the range of 1.4 to 4.9 micros. Significant enhancements of solvent proton relaxation rates were observed between 10 and 50 MHz for one of the complexes of the series [Gd(III)-DTPA-bis-2-ethylhexylamide] in human serum albumin (HSA) solution, indicating the formation of a paramagnetic macromolecular adduct. The binding association constant K(A) of the complex and the albumin 5.7 x 10(3) M(-1) was obtained, and the relaxivity of the fully bound adduct was determined to be 13.8 mM(-1) s(-1) at 20 MHz and 25 degrees C. The high value of K(A) makes the above derivative a good potential blood pool contrast agent at the physiological HSA concentration.