Analytical Sciences

Basic Design and Synthesis of Sulfonated Contrast Agents for Magnetic Resonance Imaging Based on Gadolinium Complexes

Hiroki HIFUMI,* Akihiro TANIMOTO,** Aki HONDA,* Daniel CITTERIO,* and Koji SUZUKI*

*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku, Yokohama 223-8522, Japan
**Department of Diagnostic Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan

Magnetic resonance angiography (MRA) is an imaging method to examine blood vessels based on the magnetic resonance imaging (MRI) technique. For this purpose, blood pool contrast agents have been developed to selectively increase the signal intensity of the intravascular lumen for improvement of the contrast-to-noise ratio in MR images. Here, we describe the design and the syntheses of six novel sulfonated contrast agents (KMR-Sulfo1 - 6), their chemical properties and their in vivo applications. In this study, we investigated the lipophilicity and the hydrophilicity of a gadolinium complex using a convenient two-step synthesis route, with the goal of prolonging the plasma half-life by binding mainly to human serum albumin. We confirmed that KMR-Sulfo5 fulfilled the requirements as a blood pool contrast agent: it showed a sufficient relaxivity r₁ of 5.9 mM^-1 s^-1, a long plasma half-life of 25.7 min and complete elimination from the body within 12 h after the administration.

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