19F MRI Molecular Imaging Agents
Due to fluorine’s absence in biological systems, we are developing modular proteins evolved to bind to cancer biomarkers (proteins) with high affinity, and an 19F MRI imaging domain containing fluorinated amino acids. To translate our approach to clinical field strengths, we are designing highly disordered peptide sequences to result in high intensity signals with overlapping resonances, that we term “disordered symmetry”. We have recently shown good signal-to-noise can be obtained by 19F MRI at 130 μM (e.g., peptide 3) resulting from 30 overlapping fluorine signals. Importantly, through incorporation of a base-labile fluorinated side-chain and selective incorporation of D-amino acids, peptide stability can be rationally tuned to prevent unfavorable biological and environmental accumulations-two issues not commonly addressed in the design of new fluorinated imaging agents. These imaging domains are now being bioconjugated to EGFR targeting ligands, for molecular imaging of EGFR+ breast cancer
In a parallel investigation with Professors Mike Garwood and Christy Haynes, we recently showed silica nanoparticles can be loaded with a large volume of perfluorocarbons, which have been tested as oxygen sensors for biomedical applications using 19F MRI and can in the future be tailored for molecular imaging.
For further reading see:
2. “Synthesis of intrinsically disordered fluorinated peptides for modular design of high signal 19F MRI agents.” S. E. Kirberger, S. D. Maltseva, J. C. Manulik, S. A. Einstein, B. P. Weegman, M. Garwood, W. C. K. Pomerantz*, Angew. Chem. Int. Ed. 2017, 56, 6440-44
1. “Oxygen sensing with perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles.” A. L. Lee, C. T. Gee, S. Einstein, B. Weegman, A. Juelfs, H. L. Ring, K. R. Hurley, S. M. Egger, G. Swindlehurst, M. Garwood, W. C. K. Pomerantz*, C. L. Haynes*, ACS Nano 2017, 11, 5623-32.