Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy

Abstract

Purpose: To assess the feasibility of Gadophrin-2 to trace intravenously injected human hematopoietic cells in athymic mice using magnetic resonance (MR) imaging, optical imaging (OI) and fluorescence microscopy. Materials and Methods: Mononuclear peripheral blood cells from GCSF-primed patients were labeled with Gadophrin-2 (Schering AG, Berlin, Germany), a paramagnetic and fluorescent metalloporphyrin, using established transfection techniques with cationic liposomes. The labeled cells were evaluated in vitro with electron microscopy and ICP-AES. Then, 1×106 -3×10 8 labeled cells were injected into 14 nude Balb/c mice and the in vivo cell distribution was evaluated with MR and OI before as well as 4, 24 and 48 hours (h) after intravenous injection (p.i.=post injection). Five additional mice served as controls: three mice were non-treated controls and two mice were investigated after injection of nonlabeled cells. The contrast agent effect was determined quantitatively for MR by calculating ΔSI(%)-data. After completion of in vivo imaging studies, fluorescence microscopy of excised organs was performed.

In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging

“…In addition to be tailored to specific properties of already transfected NK cells, our technique provides potential advantages compared to previously described techniques for labeling of other cell types with radioactive, fluorescent or (super-) paramagnetic markers (14)(15)(16)(17)(18)(19)(20). Our MR labeling technique is noninvasive, easy to apply, less toxic (no radiotoxic cell damage) and provides 3D imaging data with high anatomical resolution.…”

“…Currently available cell labeling techniques are based on radioactive, fluorescent or (super-)paramagnetic markers (14)(15)(16)(17)(18)(19)(20)(21). Labeling techniques with radioactive markers provide a high sensitivity but limited spatial resolution and the risk of radiotoxic cell damage (14)(15)(16)(17).…”

“…Labeling techniques with radioactive markers provide a high sensitivity but limited spatial resolution and the risk of radiotoxic cell damage (14)(15)(16)(17). Labeling techniques with fluorescent markers provide a high sensitivity, but limited anatomical resolution and are currently restricted to experimental applications (18,19). Labeling techniques with contrast agents for magnetic resonance (MR) imaging have the advantage to be less toxic than radioactive and fluorescent markers and to provide an anatomical resolution at a near microscopic level in vivo (17, 20, 4 21).…”

Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect

“…According to the percentages of stem cells reaching the carotid artery (Fig. 3B) We and others have shown that intravenous infusion of stem cells does not yield a large number of cells reaching the organ of interest primarily due to the majority of stem cells being trapped inside the lungs [9][10][11]. In an effort to increase the number of stem cells crossing over to the arterial circulation, we analyzed several experimental groups focusing on cell size and adhesion molecules as potential variables.…”

“…Consequently, intravenous infusion has been used as the route of cell delivery for a large number of preclinical studies [4][5][6] and is the route of delivery for some early clinical trials [7,8]. However, questions have been raised regarding the ability to obtain a critical number of cells to the area of injury with a systemic intravenous approach [9][10][11]. Previous studies from our laboratory using intravenous administration of mesenchymal stromal cells (MSCs) for regenerative therapy of rat brain injuries demonstrate that few MSCs reach the area of injury, and the vast majority of administered cells are trapped inside the lungs.…”