title: Multimodality imaging of endothelial progenitor cells with a novel multifunctional probe featuring positive magnetic resonance contrast and near-infrared fluorescence.
abstract: The multimodal strategy incorporating T1-weighted magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging can complement their strengths to provide images with high sensitivity and spatial resolution for noninvasively and dynamically monitoring endothelial progenitor cells (EPCs) in potential EPC-dominated therapies. Here we report the development of a protein-based imaging probe, bCD-PLL-Cy5.5 Conjugate 1, in which the bacterial cytosine deaminase (bCD) protein was modified with poly-l-lysine (PLL) that is labeled with imaging reporters, including T1-weighted MRI contrast chelator and NIR fluorophore. Conjugate 1 showed low cytotoxicity in EPCs isolated from the rabbit peripheral blood. The normalized cell viability was maintained above 90% after incubation for 1 to 5 days. Fluorescence microscopy of live cells indicated rapid cellular uptake of Conjugate 1 into EPCs in 15 minutes, and flow cytometry studies demonstrated the time-dependent internalization of Conjugate 1 with maximum uptake 48 hours after the treatment. MRI of phantoms demonstrated significant reduction of the T1 value of the EPC pellet that was pretreated with 2 μM of Conjugate 1 for 24 hours. Our preliminary data suggest that as a multimodal imaging contrast medium, Conjugate 1 offers a promising imaging probe for tracking the delivery and therapeutic response of EPCs in vivo.
authors.affiliation: Laboratory ofMolecular Imaging, Department of Radiology, Zhongda Hospital,Medical School of Southeast University, Nanjing, China. jsh0836@hotmail.com
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
authors.forename: Yiru
authors.initials: Y
authors.lastname: Qiu
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000818:Animals; D002470:Cell Survival; D043525:Cytosine Deaminase; D042783:Endothelial Cells / Q000737:chemistry* / Q000166:cytology; D029968:Escherichia coli Proteins; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D018613:Microscopy, Confocal; D011817:Rabbits; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*; D013234:Stem Cells / Q000737:chemistry* / Q000166:cytology
chemical_list: D029968:Escherichia coli Proteins; D005456:Fluorescent Dyes; D043525:Cytosine Deaminase; C468827:codA protein, E coli