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We report two conjugates of gem-diethyl pyrroline nitroxide radicals with D-mannosamine as potential metabolic organic radical contrast agents, mORCAs, circumventing the need for biorthogonal reactions. In-cell EPR spectroscopy, using Jurkat cells and analogous conjugate, based on a pyrrolidine nitroxide radical, shows an efficient incorporation of highly immobilized nitroxides, with a correlation time of τcor = 20 ns. In vivo MRI experiments in mice show that the paramagnetic nitroxide radical shortens the T1 and T2 relaxation times of protons in water located in the kidney and brain by only up to ~10% after 3 d. Ex vivo EPR spectroscopic analyses indicate that the contrast agents in mouse tissues are primarily localized in the kidney, lung, liver, heart, and blood, which primarily contain immobilized nitroxide radicals with τcor = 4–9 ns. The spin concentrations in tissues remain low (1–3 nmol g⁻1) at 24 h after the third mORCA injection, approximately one to two orders of magnitude lower than those of ORCAFluor and BASP-ORCA (measured at ~24 h post-injection). These low spin concentrations explain the small proton T1 and T2 relaxation changes observed in in vivo MRI.
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Supramolecular and biomacromolecular enhancement of metal-free magnetic resonance imaging contrast agents
Many contrast agents for magnetic resonance imaging are based on gadolinium, however side effects limit their use in some patients. Organic radical contrast agents (ORCAs) are potential alternatives, but are reduced rapidly in physiological conditions and have low relaxivities as single molecule contrast agents. Herein, we use a supramolecular strategy where cucurbit[8]uril binds with nanomolar affinities to ORCAs and protects them against biological reductants to create a stable radical in vivo . We further overcame the weak contrast by conjugating this complex on the surface of a self-assembled biomacromolecule derived from the tobacco mosaic virus.
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- Award ID(s):
- 1654405
- PAR ID:
- 10137619
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 11
- Issue:
- 8
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 2045 to 2050
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C9SC05510J
