Development of oligonucleotide‐based contrast agent with higher relaxivity

Gadolinium‐based contrast agents (GBCAs) is at present, the most widely used class of contrast agents in clinical magnetic resonance imaging (MRI). Although generally deemed to be safe, in some patients, accumulation of toxic gadolinium(III), Gd 3+ ions leading to the development of nephrogenic systemic fibrosis may occur. Our project aims to develop a GBCA with higher efficacy that can potentially result in lower toxicity. Most current clinical GBCAs are complexes composed of Gd 3+ ion chelated in an organic ligand molecule with an overall molecular weight of ~0.5 kDa. Since the efficacy (as measured by the parameter called relaxivity) of the agent is dependent on its size, we herein proposed a GBCA with significantly increased size and weight through the use of 30‐ to 40‐base long oligonucleotides as a ligand for the Gd 3+ complex, in lieu of the conventional small organic molecule. The chelation of the complex will result in an agent of ~10 kDa, which will exhibit markedly different relaxivity from that of the significantly smaller GBCAs. Using an in vitro selection procedure, an oligonucleotide strand with a high binding affinity to the complex is isolated. The relaxivity of this supramolecular construct is subsequently measured on a nuclear magnetic resonance spectrometer. Overall, this design may allow for a reduced dosage of the GBCAs which will lower the chances of Gd 3+ accumulation in tissues. Support or Funding Information California State University, East Bay Office of Research and Sponsored Programs Faculty Support Grant California State University, East Bay Center for Student Research Scholarship This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .