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

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 (18F-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 MSCTF-NP cell number and dephasing (dark) signal (R2 = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 3 107 cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R2 = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R2 = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 3 108 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.