TY - JOUR
T1 - Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter
AU - Chang, Connie
AU - Chan, Angel
AU - Lin, Xiaoping
AU - Higuchi, Takahiro
AU - Terrovitis, John
AU - Afzal, Junaid M.
AU - Rittenbach, Andrew
AU - Sun, Dongdong
AU - Vakrou, Styliani
AU - Woldemichael, Kirubel
AU - O'Rourke, Brian
AU - Wahl, Richard
AU - Pomper, Martin
AU - Tsui, Benjamin
AU - Abraham, M. Roselle
PY - 2013/2/1
Y1 - 2013/2/1
N2 - 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.
AB - 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.
KW - metabolism
KW - molecular imaging
KW - stem cell
UR - http://www.scopus.com/inward/record.url?scp=84873410039&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.112.273375
DO - 10.1161/CIRCRESAHA.112.273375
M3 - Article
C2 - 23255420
AN - SCOPUS:84873410039
SN - 0009-7330
VL - 112
SP - 441
EP - 450
JO - Circulation research
JF - Circulation research
IS - 3
ER -