Zhaoda Zhang1, Matthew Greenfield2, Andrew Kolodziej2, Peter Caravan1
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA, United States; 2Epix Pharmaceuticals, Lexington, MA, United States
Fibrin-specific peptides conjugated to multiple Gd-chelates, e.g. EP-2104R and EP-1242, have shown efficacy in MR detection of thrombus. We hypothesized that a second small binding group at the N-terminus may provide additional fibrin affinity, while at the same time would restrict internal motion at the N-terminus upon fibrin binding and this would result in higher relaxivity. We demonstrate that a minor perturbation (addition of a thymine moiety at the N-terminus) in probe structure can result in a 50% increase in relaxivity at the target, but does not increase off-target relaxivity. This heteroditopic binding approach is generalizable to other protein-targeted probes.