Manganese Steps In For Safer Contrast

Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used to evaluate medical issues ranging from a tag football knee injury to blood clots in the kidneys. As useful as these techniques are, people with substantial kidney and renal artery problems are often excluded from their use because the iodinated and gadolinium-based contrast agents required can cause further damage or unwanted toxicity. Researchers have been seeking safe alternatives, such as manganese complexes. But the versions developed so far have not been stable enough to prevent displacement of manganese by other metals or able to meet other criteria such as quickly being eliminated from the body. Eric M. Gale, Peter Caravan, and colleagues at the A. A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital decided to sit down and design a new type of manganese chelating ligand that could provide a solution (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b10748). The ligand, which they call PyC3A, creates a chelating environment highly resistant to manganese dissociation, can include functional groups for binding targeted tissues, and quickly clears from the body. The team synthesized PyC3A in five steps and reports that a fibrin-targeted derivative of the manganese contrast agent shown provides images of rat arterial blood clots comparable to the best gadolinium contrast agent without any apparent toxicity.