Magnetic Field Dependence of Longitudinal Relaxation Rates of Solutions of Various Protein-Gadolinium3+ Chelate Conjugates

Abstract

Bovine serum albumin (BSA) and porcine serum fibrinogen (FIB) were multiply labeled with gadolinium3+ by using three different ligands: DTPA dianhydride, isothio-cyanato-benzyl-DTPA (ITCB-DTPA), in which none of the five coordinating carboxylates is employed for macromolecular linkage, and isothiocyanatobenzyl-TRITA, a macrocyclic ligand. The nuclear magnetic resonance dispersion (NMRD) profiles of the protein-(Gd chelate) conjugates were characteristic to each chelate involved, possessing, as expected, greater longitudinal relaxivities than the corresponding Gd chelates alone and exhibiting prominent peaks at the proton Larmor frequency range of 10 to 40 MHz. Particularly favorable relaxation enhancement was measured in the solutions of BSA-(ITCB-DTPA-Gd) at this field range. When the number of chelates conjugated with protein increased, up to 163 Gd chelates per one fibrinogen, a progressive decrease in relaxivity was observed. This study demonstrates the relaxation properties of novel macromolecular contrast agents designed for magnetic resonance imaging.