19F MRI Imaging of Polymer Nanogels Aided by Improved Segmental Mobility of Embedded Fluorine Moieties
Department of Radiology; Laboratory of Molecular Imaging Probes; Chemical Biology Interface Program
Biochemistry | Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Nanomedicine | Radiology
Using fluorinated probes for 19F MRI imaging is an emerging field with potential utility in cellular imaging and cell tracking in vivo, which complements conventional 1H MRI. An attractive feature of 19F-based imaging is that this is a bio-orthogonal nucleus and the naturally abundant isotope is NMR active. A significant hurdle however in the 19F MRI arises from the tendency of organic macromolecules, with multiple fluorocarbon substitutions, to aggregate in the aqueous phase. This aggregation results in significant loss of sensitivity, because the T2 relaxation times of these aggregated 19F species tend to be significantly lower. In this report, we have developed a strategy to covalently trap nanoscopic states with an optimal degree of 19F substitutions, followed by significant enhancement in T2 relaxation times through increased segmental mobility of the side chain substituents facilitated using stimulus-responsive elements in the polymeric nanogel. In addition to NMR relaxation time based evaluations, the ability to obtain such signals are also evaluated in mouse models. The propensity of these nanoscale assemblies to encapsulate hydrophobic drug molecules and the availability of surfaces for convenient introduction of fluorescent labels suggest the potential of these nanoscale architectures for use in multi-modal imaging and therapeutic applications.
DOI of Published Version
Biomacromolecules. 2018 Dec 18. doi: 10.1021/acs.biomac.8b01383. [Epub ahead of print] Link to article on publisher's site
Munkhbat, Oyuntuya; Canakci, Mine; Zheng, Shaokuan; Hu, Weiguo; Osborne, Barbara; Bogdanov, Alexei A.; and Thayumanavan, S., "19F MRI Imaging of Polymer Nanogels Aided by Improved Segmental Mobility of Embedded Fluorine Moieties" (2018). Radiology Publications and Presentations. 438.