Multilocus Binding Increases the Relaxivity of Protein-Bound MRI Contrast Agents

✍ Scribed by Zhaoda Zhang; Matthew T. Greenfield; Marga Spiller; Thomas J. McMurry; Randall B. Lauffer; Peter Caravan

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 121 KB
• Volume: 44
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200502245

✦ Synopsis

on the occasion of his 60th birthday

The utility of clinical magnetic resonance imaging (MRI) has been greatly expanded by the use of contrast agentsgadolinium complexes that serve to increase the longitudinal nuclear relaxation rate (1/T 1 ) of water protons. Commercial contrast agents are only effective at high concentrations (> 0.1 mm) and, as a result, there has been considerable effort to increase their sensitivity. One approach is to increase the number of gadolinium ions in the molecule by making polymeric or dendrimeric contrast agents. [1] A second approach is to optimize the parameters that influence relaxation enhancement, such as rotational diffusion and water exchange. [2] An effective mechanism for increasing relaxivity (r 1 = (D1/T 1 )/[Gd]) is the receptor-induced magnetizationenhancement (RIME) effect. [3] An example is the GdDTPA derivative MS-325, which targets serum albumin. When MS-325 binds to albumin, the rotational correlation time (t R ) increases from that of a small molecule to that of the protein,