Todd C. Soesbe1, 2, S. James Ratnaker1, Zoltan Kovacs1, A. Dean Sherry1, 3
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States; 2Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States; 3Department of Chemistry, The University of Texas at Dallas, Richardson, TX, United States
Magnetic resonance imaging (MRI) offers superior anatomic resolution and soft tissue contrast compared to x-ray computed tomography, making it an excellent tool for cancer prevention studies. It was recently shown that lanthanide-based Ln3+DOTA chelates (Ln3+ ≠ La3+, Gd3+, Lu3+) create enhanced negative contrast (i.e., darkening) in MRI through the chemical exchange of water molecules. The level of this T2-exchange contrast, which adds to the inherent paramagnetic T2 contrast of the Ln3+ ion, reaches a maximum at a specific water molecule exchange rate. It was also recently demonstrated that T2-exchange contrast could be increased by several orders of magnitude through simple linear polymerization of the Ln3+DOTA chelate. We hypothesize that by using these methods a highly sensitive molecule-sized T2 contrast agent can be created. The transverse relaxivity (r2) would be an order of magnitude greater than any currently existing contrast agent (e.g., super paramagnetic iron oxide nanoparticles), while retaining the advantages of using small molecules rather than nanoparticles for improved biological targeting, uptake, and clearing.