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The development of metal-free magnetic resonance imaging (MRI)agents demands precise control over molecular architecture to achieve optimal performance. Current fluorine-based contrast agents rely on maximizing fluorine content (>20 wt %) for sensitivity, requiring extensive solubilizing groups that lead to signal-diminishing aggregation. Here we show that discrete brush polymers (Đ= 1.0) with precise backbone lengths and a single terminal fluorine group achieve superior imaging performance through architectural control rather than high fluorine content. This design prevents both intra- and intermolecular fluorine aggregation while maintaining high aqueous solubility, enabling sharper signals and higher sensitivity than conventional systems despite containing less than 7 wt %fluorine. Systematic investigation reveals how backbone length controls fluorine mobility and signal generation, establishing clear structure−property relationships previously obscured by molecular heterogeneity. This work demonstrates how precise architectural control can enhance functional performance beyond traditional approaches, providing new strategies for designing imaging materials.
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A Multifunctional Contrast Agent for 19 F-Based Magnetic Resonance Imaging
Magnetic resonance imaging, MRI, relying on 19F nuclei has attracted much attention, because the isotopes exhibit a high gyromagnetic ratio (comparable to that of protons) and have 100% natural abundance. Furthermore, due to the very low traces of intrinsic fluorine in biological tissues, fluorine labeling allows easy visualization in vivo using 19F-based MRI. However, one of the drawbacks of the available fluorine tracers is their very limited solubility in water. Here, we detail the design and preparation of a set of water-compatible fluorine-rich polymers as contrast agents that can enhance the effectiveness of 19F-based MRI. The agents are synthesized using the nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) copolymer and a mixture of amine-appended fluorine groups and polyethylene glycol (PEG) blocks. This allows control over the polymer architecture and stoichiometry, resulting in good affinity to water solutions. We further investigate the effects of introducing additional segmental mobility to the fluorine moieties in the polymer, by inserting a PEG linker between the moieties and the polymer backbone. We find that controlling the polymer stoichiometry and introducing additional segmental mobility enhance the NMR signals and narrow the peak profile. In particular, we assess the impact of the PEG linker on T2* and T1 relaxation times, using a series of gradient-recalled echo images with varying echo times, TE, or recovery time, TR, respectively. We find that for equivalent concentrations, the PEG linker greatly increases T2*, while maintaining high T1 values, as compared to polymers without this linker. Phantom images collected from these compounds show bright signals over a background with high intensities.
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- Award ID(s):
- 2005079
- PAR ID:
- 10406486
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Bioconjugate Chemistry
- Volume:
- 33
- Issue:
- 5
- ISSN:
- 1043-1802
- Page Range / eLocation ID:
- 881 to 891
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1021/acs.bioconjchem.2c00116
