Tissue Relaxation Enhancement after Intravenous Administration of (ITCB-DTPA)-Gadolinium Conjugated Albumin, an Intravascular Magnetic Resonance Imaging Contrast Agent

Gadolinium-isothiocyanato-benzyl-diethylenetriamine pentaacetic acid (ITCB-DTPA-Gd), a derivative of Gd-DTPA, was multiply conjugated to bovine serum albumin (BSA). In the synthesis of BSA-(ITCB-DTPA-Gd) conjugate, none of the five carboxylate groups of DTPA is functionalized for protein-chelate linkage. The rationale for this modification is to improve the affinity for Gd3+. We obtained a high-stability constant for the complex, comparable to unbound Gd-DTPA. Also, the complex had a T1 relaxivity as high as 30.3 seconds-1mmol-1 at 29 MHz (at 24 degrees C). At this field strength, and T1 of rat blood declined 91% after injection of 300 mg/kg of BSA-(ITCB-DTPA-Gd), corresponding to a Gd dose of 0.02 mmol/kg, while at 0.86 MHz it declined 64%. The shortening of T1 in vitro of blood, as well as spleen, lungs, and kidneys, persisted for 60 minutes. Better enhancement on post-contrast magnetic resonance images of rats was obtained at 1.0 T than at 0.04 T. Tissues with rich vascularization and large venous structures were well displayed at the higher field.