| Autor: |
Lumata JL; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Hagge LM; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu.; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA., Gaspar MA; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Trashi I; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Ehrman RN; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Koirala S; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Chiev AC; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Wijesundara YH; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Darwin CB; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Pena S; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA., Wen X; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA., Wansapura J; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA., Nielsen SO; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu., Kovacs Z; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA., Lumata LL; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA.; Department of Physics, The University of Texas at Dallas, USA., Gassensmith JJ; Department of Chemistry and Biochemistry, The University of Texas at Dallas, USA. gassensmith@utdallas.edu.; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, USA.; Department of Bioengineering, The University of Texas at Dallas, USA. |
| Abstrakt: |
Superoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection strategies have led to the exploration of organic-based contrast agents for magnetic resonance imaging (MRI). This study compares the effectiveness of two such agents, nTMV-TEMPO and kTMV-TEMPO, for detecting superoxide in a mouse liver model with lipopolysaccharide (LPS)-induced inflammation. The study demonstrates that kTMV-TEMPO, with a strategically positioned lysine residue for TEMPO attachment, outperforms nTMV-TEMPO as an MRI contrast agent. The enhanced sensitivity of kTMV-TEMPO is attributed to its more exposed TEMPO attachment site, facilitating stronger interactions with water protons and superoxide radicals. EPR kinetics experiments confirm kTMV-TEMPO's faster oxidation and reduction rates, making it a promising sensor for superoxide in inflamed liver tissue. In vivo experiments using healthy and LPS-induced inflamed mice reveal that reduced kTMV-TEMPO remains MRI-inactive in healthy mice but becomes MRI-active in inflamed livers. The contrast enhancement in inflamed livers is substantial, validating the potential of kTMV-TEMPO for detecting superoxide in vivo . This research underscores the importance of optimizing contrast agents for in vivo imaging applications. The enhanced sensitivity and biocompatibility of kTMV-TEMPO make it a promising candidate for further studies in the realm of medical imaging, particularly in the context of monitoring oxidative stress-related diseases. |
