Customizable, multi-functional fluorocarbon nanoparticles for quantitative in vivo imaging using 19F MRI and optical imaging.
Monitoring cell trafficking in vivo noninvasively is critical to improving cellular therapeutics, drug delivery, and understanding disease progression. In vivo imaging, of which magnetic resonance imaging (MRI) is a key modality, is commonly used for such monitoring. (19)F MRI allows extremely specific detection and quantification of cell numbers directly from in vivo image data, longitudinally and without ionizing radiation. We used fluorocarbons previously used in blood substitutes and imaging agents for ultrasound and computed tomography to synthesize monodisperse nanoparticles that are stable at 37 degrees C and can be frozen for storage. These large (19)F labeling compounds are insoluble in aqueous environments and often emulsified, typically forming emulsions unsuitable for long-term storage. Instead, we used a non-toxic polymer already in clinical use, poly(D,L-lactide-co-glycolide), to encapsulate a range of (19)F compounds. These nanoparticles can be customized in terms of content (imaging agent, fluorescent dye, drug), size (200-2000 nm), coating (targeting agent, antibody) and surface charge (-40 to 30 mV). We added a fluorescent dye and antibody to demonstrate the versatility of this modular imaging agent. These nanoparticles are adaptable to multimodal imaging, although here we focused on MRI and fluorescence imaging. Here, we imaged primary human dendritic cells, as used in clinical vaccines.
Srinivas
Mangala
M
Department of Tumor Immunology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Cruz
Luis J
LJ
Bonetto
Fernando
F
Heerschap
Arend
A
Figdor
Carl G
CG
de Vries
I Jolanda M
IJ
D000818:Animals; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods*; D005461:Fluorine / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*
D005466:Fluorocarbons; D005461:Fluorine