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Radiology. 2016 Sep;280(3):826-36. doi: 10.1148/radiol.2016151150. Epub 2016 Jun 22.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

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From the Department of Radiology, James Clark Center, Molecular Imaging Program at Stanford, 318 Campus Drive West, Room E153, Stanford University, Stanford, CA 94305 (N.P., K.Z., K.I., R.P., J.K.W., D.Y., M.P., Y.F.C., F.H., S.Y., S.S.G.); Department of Cardiovascular Medicine (J.C., F.I., J.K.L., T.T., H.K., C.N.D., M.M., R.D., P.C.Y., T.J.B., P.G.Y., M.V.M.), Department of Cardiothoracic Surgery (J.C.S., D.R.M., J.E.C., A.B.G., R.C.R.), Department of Bioengineering (D.Y., P.G.Y., S.S.G.), Canary Center for Early Detection of Cancer (R.P., S.S.G.), and Department of Materials Science and Engineering (S.S.G.), Stanford University, Stanford, Calif; GE Global Research Center, General Electric, Niskayuna, NY (S.B.); Department of Nuclear Medicine, Kyungpook National University, Daegu, South Korea (B.C.A.); and Advanced Center for Treatment, Research, and Education ACTREC, Tata Memorial Centre, Navi Mumbai, India (P.R.).


Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (

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