Cheng Zhang,1,2 Shehzahdi Shebbrin Moonshi,1,2 Yanxiao Han,4 Simon Puttick,1,2 Hui Peng,1,2 Bryan John Abel Magoling,1 James C. Reid,1 Stefano Bernardi,1 Debra J. Searles,1,3 Petr Král,4,5,6 and Andrew K. Whittaker1,2*

 

1Australian Institute for Bioengineering and Nanotechnology, 2ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, 3School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane Qld 4072, Australia.
4 Department of Chemistry, 5 Department of Physics,
6 Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois,  USA.

 

  19F magnetic resonance imaging (MRI) is a powerful noninvasive molecular imaging technique for the detection of important diseases. The major challenge of 19F MRI is signal attenuation caused by the reduced solubility and mobility of probes with increased number of fluorine atoms. Here we report the synthesis of perfluoropolyether (PFPE) end-functionalized homopolymer of oligo(ethylene glycol) methyl ether acrylate (poly(OEGA)n-PFPE) for the development of highly sensitive 19F MRI contrast agents (CAs). The structural characteristics, conformation/aggregation behaviour, 19F NMR longitudinal and transverse relaxation times (T1 and T2) and 19F MRI were studied in detail for the poly(OEGA)n-PFPE polymers. Dynamic light scattering (DLS) and molecular dynamics (MD) simulations were conducted and demonstrated that the poly(OEGA)20-PFPE polymer undergoes single-chain folding in water while poly(OEGA)10-PFPE and poly(OEGA)4-PFPE polymers experience multiple-chain aggregation. Long 19F T2 relaxation times were obtained for all poly(OEGA)-PFPE polymers (> 85 ms) and no obvious decrease in 19F T2 was observed with increasing fluorine content up to ~30 wt %. Moreover, the signal-to-noise ratio increased linearly with increasing concentration of fluorine, indicating that the PFPE-based polymers can be applied as quantitative tracers. Furthermore, we investigated the in vivo behaviour, in particular their biodistribution, of the polymers with different aggregation properties. Control over the balance of hydrophobicity and hydrophilicity allows manipulation of the aggregation state and this leads to different circulation behaviour in a murine model (Figure 1). This first report of the synthesis of polymeric PFPE-based 19F MRI CAs demonstrates that these polymers are an exciting new class of 19F MRI CAs with extremely high fluorine content and outstanding imaging sensitivity.

Figure 1:  The PFPE-based polymers for in vivo 19F MRI and fluorescence imaging.

Biographic Details

Dr. Cheng Zhang

Australian Institute for Bioengineering

and Nanotechnology, Australia.

Phone: (+61) 406 144 492

E-mail: cheng.zhang2@uqconnect.edu.au

Research interests: Polymeric biomateirals, NMR and MRI