Development of Timd2 as a Reporter Gene for MRI
Patrick, P Stephen
Rodrigues, Tiago B
Kettunen, Mikko I
Lyons, Scott K
Magnetic Resonance in Medicine
Wiley on behalf of International Society for Magnetic Resonance in Medicine.
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Patrick, P. S., Rodrigues, T. B., Kettunen, M. I., Lyons, S. K., Neves, A., & Brindle, K. (2015). Development of Timd2 as a Reporter Gene for MRI. Magnetic Resonance in Medicine https://doi.org/10.1002/mrm.25750
Purpose: To assess the potential of an MRI gene reporter based on the ferritin receptor Timd2 (T-cell immunoglobulin and mucin domain containing protein 2), using T1- and T2- weighted imaging. Methods: Pellets of cells that had been modified to express the Timd2 transgene, and incubated with either iron-loaded or manganese-loaded ferritin, were imaged using T1- and T2- weighted MRI. Mice were also implanted subcutaneously with Timd2-expressing cells and the resulting xenograft tissue imaged following intravenous injection of ferritin using T2- weighted imaging. Results: Timd2-expressing cells, but not control cells, showed a large increase in both R2 and R1 in vitro following incubation with iron-loaded and manganese-loaded ferritin, respectively. Expression of Timd2 had no effect on cell viability or proliferation; however, manganese-loaded ferritin, but not iron-loaded ferritin, was toxic to Timd2-expressing cells. Timd2-expressing xenografts in vivo showed much smaller changes in R2 following injection of iron-loaded ferritin than the same cells incubated in vitro with iron-loaded ferritin. Conclusion: Timd2 has demonstrated potential as an MRI reporter gene, producing large increases in R2 and R1 with ferritin and manganese-loaded ferritin respectively in vitro, although more modest changes in R2 in vivo. Manganese-loaded apoferritin was not used in vivo due to the toxicity observed in vitro.
ferritin, manganese, T1-weighted, T2-weighted, reporter gene
This work was supported by the Medical Research Council and Cancer Research UK (CRUK) doctoral training grants (to P.S.P.) and a CRUK Program Grant to K.M.B. T.B.R. was in receipt of Intra-European Marie Curie and Long-Term European Molecular Biology Organization fellowships.
Cancer Research UK (16465)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
External DOI: https://doi.org/10.1002/mrm.25750
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248607
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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