MRI is a powerful, non-invasive tool for studying biological systems in vivo. Because the clinically used 1H MRI suffers from a large background signal, 19F MRI has garnered attention in recent years. There have been a variety of small molecule and polymeric contrast agents developed for 19F MRI, but none have been routinely adopted. Fluorinated small molecules have poor aqueous solubility, necessitating emulsions that can be polydisperse and have poor reproducibility. Polymeric contrast agents suffer from low fluorine content, short spin-spin relaxation times (causing signal attenuation), and complex syntheses. Recently, the Johnson group has developed a brush-arm star polymer (BASP) platform that can deliver a high concentration of organic radical contrast agents to tumors for 1H MRI in vivo. BASPs are relatively non-toxic and can be readily produced on kilogram scale, prompting their current evaluation in preclinical trials in mice. In this proposal, we aim to create a series of novel fluorinated BASPs (F-BASPs) with well-defined particle size, polydispersity, and fluorine content. Poly(ethylene glycol) will be used to impart water solubility and high fluorine concentrations will be achieved through the use of a ?triple-click? branched macromonomer base, which contains three pendant alkyne moieties to which fluorine tags can be tethered using copper-catalyzed click chemistry. The particles will be fully characterized by NMR, GPC, DLS, and TEM while being evaluated in vitro for toxicity, solubility, and suitability for MRI using phantoms. The most promising F-BASP will then be evaluated in vivo, including toxicity, pharmacokinetics, biodistribution, and, ultimately, 19F MRI in mice. The modularity of this system will allow us to readily address the typical challenges of 19F MRI contrast agents ? such as aggregation, solubility, and fluorine concentration ? in a synthetically straight forward manner. The development of these F-BASPs will provide the groundwork for metal-free, easily synthesized contrast agents to make 19F MRI viable for clinical use.
19F MRI is a promising non-invasive and non-radiative diagnostic tool, but current 19F contrast agents suffer from low fluorine content, difficult syntheses, and poor solubility. Through the synthesis of well-defined, fluorinated brush-arm star polymers, the proposed research will establish a scalable, modular platform of highly fluorinated nanoparticles aimed at addressing current limitations of 19F MRI to meet the needs of the health industry.
