Development of Intravascular Contrast Agents for MRI Using Gadolinium Chelates

Abstract

Two MRI contrast agents (CAs) composed of Gd-DO3A conjugated to amino acid building blocks derived from glutamic acid (CA1) and lysine (CA2) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mm. The longitudinal relaxivities (r(1)) of CA1 and CA2 measured at 9.4 T are 6.4 and 5.4 mm(-1) s(-1) in H(2)O at 25 degrees C, respectively. Both r(1) values are higher than those of CAs in clinical use: Gd-DTPA (Magnevist, Bayer Schering, Germany) and Gd-DOTA (Dotarem, Guerbet, France). In vivo imaging in Wistar rats demonstrated considerable signal enhancement (similar to 50%) in the brain artery by CA2, but lower signal enhancement (similar to 30%) by CA1. In contrast to Dotarem, which showed a similar signal enhancement as CA2, the enhancement by CA2 remained high (similar to 30%), even at 52 min post-injection. This demonstrates that CA2 has a much longer blood half-life (68.1 min), which could be advantageous for angiography and tissue targeting.