| RESEARCH |
Toward Imaging Tumor Growth MRI contrast agent may provide clear images of new blood vessel formation BETHANY HALFORD Keeping track of growing tumors could get easier, thanks to a new magnetic resonance imaging (MRI) contrast agent that's designed to target blood vessel formation. Use of the compound may lead to earlier detection of tumors, according to the team of Dutch researchers who developed it (Chem. Commun. 2005, 2811). ON TARGET Contrast agent brings together a Gd(III) chelate to provide MRI contrast, a cyclic tripeptide to target angiogenesis, and biotin to hook the molecule onto avidin. Although MRI is one of medicine's most powerful, noninvasive diagnostic tools, the technology's sensitivity is dictated by contrast agents, which enhance the way the instrument images different types of tissue. Until now, no MRI contrast agent provided clear images of angiogenesis, or new blood vessel growth. Because formation of new blood vessels around a tumor usually indicates tumor growth, a research group led by E. W. (Bert) Meijer and Anouk Dirksen of Eindhoven University of Technology and Tilman M. Hackeng of the University of Maastricht thought that an angiogenesis-targeting contrast agent could offer physicians a powerful diagnostic tool. They designed a small molecule that couples a gadolinium(III) chelate--a common contrast agent motif--with a cyclic tripeptide known to bind specifically to an enzyme that's overexpressed in growing blood vessels. The Dutch researchers decided they could boost the MRI sensitivity to this contrast agent by tying several of these small molecules to one carrier, thereby ensuring high local concentrations of gadolinium ions at the point of angiogenesis. They picked the protein avidin as this carrier because it forms a supramolecular complex with four molecules of biotin. By covalently incorporating the biotin structure into their contrast agent molecule, they were able to create an angiogenesis-targeting contrast agent incorporating four Gd ions. According to Meijer, the researchers are currently testing the supramolecular complex in mice. |
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