Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter

Connie Chang, Angel Chan, Xiaoping Lin, Takahiro Higuchi, John Terrovitis, Junaid M. Afzal, Andrew Rittenbach, Dongdong Sun, Styliani Vakrou, Kirubel Woldemichael, Brian O'Rourke, Richard Wahl, Martin Pomper, Benjamin Tsui, M. Roselle Abraham

Research output: Contribution to journalArticle

Abstract

RATIONALE:: Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes. OBJECTIVE:: The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtained by firefly luciferase and human sodium-iodide symporter labeling of cardiosphere-derived cells were investigated. METHODS AND RESULTS:: Fluorodeoxyglucose uptake, ATP levels, Tc-pertechnetate uptake, and bioluminescence were measured in vitro in adherent and suspended cardiosphere-derived cells. In vivo dual-isotope single-photon emission computed tomography/computed tomography imaging or bioluminescence imaging (BLI) was performed 1 hour and 24 hours after cardiosphere-derived cell transplantation. Single-photon emission computed tomography quantification was performed using a phantom for signal calibration. Cell loss between 1 hour and 24 hours after transplantation was quantified by quantitative polymerase chain reaction and ex vivo luciferase assay. Cell dissociation followed by suspension for 1 hour resulted in decreased glucose uptake, cellular ATP, Tc uptake, and BLI signal by 82%, 43%, 42%, and 44%, respectively, compared with adherent cells, in vitro. In vivo Tc uptake was significantly lower at 1 hour compared with 24 hours after cell transplantation in the noninfarct (P<0.001; n=3) and infarct (P<0.001; n=4) models, despite significant cell loss during this period. The in vivo BLI signal was significantly higher at 1 hour than at 24 hours (P<0.01), with the BLI signal being higher when cardiosphere-derived cells were suspended in glucose-containing medium compared with saline (PBS). CONCLUSIONS:: Adhesion is an important determinant of cellular bioenergetics, Tc-pertechnetate uptake, and BLI signal. BLI and sodium-iodide symporter imaging may be useful for in vivo optimization of bioenergetics in transplanted cells.

Original languageEnglish (US)
Pages (from-to)441-450
Number of pages10
JournalCirculation research
Volume112
Issue number3
DOIs
StatePublished - Feb 1 2013

Keywords

  • metabolism
  • molecular imaging
  • stem cell

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Chang, C., Chan, A., Lin, X., Higuchi, T., Terrovitis, J., Afzal, J. M., Rittenbach, A., Sun, D., Vakrou, S., Woldemichael, K., O'Rourke, B., Wahl, R., Pomper, M., Tsui, B., & Abraham, M. R. (2013). Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter. Circulation research, 112(3), 441-450. https://doi.org/10.1161/CIRCRESAHA.112.273375