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Abstract:
Introduction
Overhauser MRI is a technique, which could enable in vivo magnetic resonance experiments at low (<0.5 T) and ultralow (<10 mT) fields. The higher spin order of electrons is transferred to e.g. protons. Enhancement factors >100 can be achieved. This technique requires a stable free electron source in mM concentrations, usually in the form of free radicals. To enhance the stability of free radicals one can use nanosized carrier molecules. Here, we present cyclodextrines as carriers for nitroxide free radicals. The Overhauser DNP performance as well as toxicity and stability are tested.
Methods
We tested biotin, avidin, dendrimers, liposomes and cyclodextrines as carriers for different nitroxide free radicals.
To assess the ODNP performance, the maximum enhancement Emax and the RF power P1/2, needed to reach Emax/2, were measured at 2 mM concentration (a reasonable concentration for in vivo experiments) in a homemade ULF MRI system.
The stability of the selected nitroxides in the aforementioned carriers was tested in ascorbic acid solution and whole blood using EPR and ULF NMR spectroscopy. Cell viability was monitored on rat astrocyte cell cultures using the MTT assay and propidium iodide (PI) staining. Results obtained from probes with and without carriers were compared for commercially available nitroxides 3CP, 3CxP and TEMPOL and synthesized nitroxides.
Results/Discussion
Except for cyclodextrines all other carrier systems showed poor Overhauser DNP properties with nitroxides embedded into them. An increase of spectral line broadening, or lower tumbling rates of the larger carriers seem to be the reasons for the significant drop in ODNP performance.
Cyclodextrines with nitroxides showed a reasonable enhancement with improved water solubility enabling the use of lipophilic radicals. A stability improvement of up to 30% in the presence of ascorbic acid was measured via ULF NMR spectroscopy.
Some nitroxides with γ-cyclodextrin showed reduction in cell viability experiments as seen by PI staining and a decrease in metabolic activity as revealed by the MTT assay, however, these effects were ascribed mostly to the vehicle itself.
Conclusions
Even though most carrier systems decrease the ODNP efficiency, cyclodextrine-based radicals seem to be a promising candidate for future ultralow field Overhauser MRI in vivo experiments and high field T1 contrast agents. They show improved stability compared to nitroxides without carrier systems.
Further investigations should show, if only lipophilic nitroxides benefit from being embedded into cyclodextrine.
Acknowledgement
This work was supported with ERA.Net RUS+ project ST2017-382: NanoHyperRadicals (including RFBR 18-53-76003-ERA-A).
Disclosure
I or one of my co-authors have no financial interest or relationship to disclose regarding the subject matter of this presentation.
