Use of lipophilic near-infrared dye in whole-body optical imaging of hematopoietic cell homing

Kalchenko, Vyacheslav; Malina, Victoria; Lapid, Kfir; Haramati, Sharon; Lapidot, Tsvee; Brill, Alexander; Harmelin, Alon

doi:10.1117/1.2364903

Cited by 101 publications

(81 citation statements)

References 12 publications

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“…There is a need to visualize the migration of immune cells injected into living animals and we achieved this by using a new near-infrared fluorescent dye, DiR (1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide), although the use of DiR as an in vivo cell tracer is still in its initial experimental stages. Kalchenko et al (6) successfully used DiR to stain human leukemia G2L cells, mouse lymphocytes and rat red blood cells for in vivo tracer experiments. Granot et al (7) also used DiR to mark fibroblast cells, which were then observed targeting to an ovarian cancer tumor some distance away from the injection site.…”

Section: A B Discussionmentioning

confidence: 99%

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

Wang

Ning

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic, however, the distribution of immune cells injected into a tumor-bearing body is unclear. In this study, we investigated the tumor-targeting capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with the near-infrared fluorescent dye DiR. As expected, no significant change in the proliferation rate or antitumor activity of CIK cells and CTLs was noted after labeling with DiR. Furthermore, a gastric carcinoma orthotopic model was established using a fibrinogen-thrombin method in nude mice followed by intraperitoneal infusion of the labeled immune cells into nude mice with established gastric carcinoma. Dynamic tracing of the immune cells was performed using a fluorescencebased live imaging system. Concentrated fluorescence signals were observed for a minimum of two weeks at the tumor site in mice infused with either CIK cells or CTLs with a peak signal at 48 h. Notably, CTLs were more persistent at the tumor site and exhibited a more intense antitumor activity than CIK cells following infusion. These results provided visual evidence of the tumor-targeting capacity of immune cells in live animals.

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Section: A B Discussionmentioning

confidence: 99%

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

Wang

Ning

et al. 2012

Experimental and Therapeutic Medicine

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“…With new imaging technology at hand, this approach can now be directly translated into in vivo imaging models. DiR has previously been used to label lymphocytes and erythrocytes and monitor the homing of these cells to different organs for up to 96 h after intravenous injection into mice using 2-dimensional reflectance imaging (22). The specificity of homing was verified, and no toxicity was observed in this study.…”

Section: Discussionmentioning

confidence: 81%

In Vivo Optical Imaging of Cellular Inflammatory Response in Granuloma Formation Using Fluorescence-Labeled Macrophages

Eisenblätter¹,

Ehrchen²,

Varga³

et al. 2009

J Nucl Med

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Near-infrared imaging such as fluorescence reflectance imaging (FRI) and fluorescence-mediated tomography (FMT) yields high signal-to-noise ratios (SNRs) and should thus be well suited for cell-tracking studies. Extravasation of monocytes or macrophages (Mfs) is one of the earliest events in inflammation. The purpose of this study was to assess whether FRI and FMT allow for the visualization and quantification of early inflammatory processes by tracing the migration of fluorescence-labeled murine Mfs in a cutaneous granuloma model. Methods: Mfs were labeled with a membrane-selective carbocyanine dye (1,3,3,). Cellular viability and function (nitric oxide production, phagocytosis, adherence) were assessed in vitro. Local inflammation was induced in mice by the subcutaneous injection of polyacrylamide gel pellets including or excluding a strong inflammatory stimulus (lipopolysaccharide). Labeled Mfs were injected intravenously, and FRI and FMT were performed up to 7 d. SNRs were calculated for the pellets, and the 3-dimensional distribution of Mfs was assessed using FMT. Cells were harvested from gel pellets and analyzed by flow cytometry. Results: DiR labeling did not affect cell viability or cell function. FRI revealed the migration of labeled Mfs into gel pellets and the homing of Mfs to different body compartments. The lipopolysaccharide-containing pellets exhibited significantly higher SNRs than did pellets without lipopolysaccharide. FMT showed that Mfs distributed mainly in the periphery of the pellets. Opt ical imaging is an appealing concept for studying cell migration in vivo. Specifically, in the near-infrared range (NIR) background fluorescence is minimal, yielding excellent signal-to-noise ratios (SNRs) and thus high sensitivity of the technique for detecting even small amounts of cells. Further, fluorophores emitting in the NIR can sufficiently penetrate the tissue, even from deeper sections, and allow detection over a longer time (1). Moreover, imaging techniques for optical imaging are rapidly developing, ranging from simple surface-weighted reflection (fluorescence reflectance imaging [FRI]) to fluorescence-mediated tomography (FMT) approaches. The latter technology is capable of delivering quantitative information on 3-dimensional fluorochrome distribution in vivo.The recruitment of immune cells and especially monocytes from the blood into tissue is crucial for the development and maintenance of inflammation (2). Interference with the mechanisms of monocyte extravasation represents an emerging new therapeutic strategy (3,4). After extravasation, monocytes can differentiate into macrophages and dendritic cells. They are crucial for nearly every step of an immune reaction including the initiation of inflammation, clearance of infectious agents or tumor cells, initiation of an adaptive immune response, and resolution of inflammation (5,6).Thus, the noninvasive tracing and monitoring of monocytes or macrophages (Mfs) in vivo by optical imaging could allow for the better localization, visualization, and

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“…It has been reported that the two 18 carbon chains of DiR could insert into the liposome membrane, resulting in specific and stable liposome staining, with negligible dye transfer between liposomes and tissue cells. 33 …”

Section: Results and Discussion Preparation Of Sbs Vpg And Sbs Dir Vpgmentioning

confidence: 99%

Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

Chen¹,

Huang²,

Wong³

et al. 2012

IJN

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Purpose:The main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration. Methods: SBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett-Rössler method. Results: SBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours. Conclusion:The overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect.

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Use of lipophilic near-infrared dye in whole-body optical imaging of hematopoietic cell homing

Cited by 101 publications

References 12 publications

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

In Vivo Optical Imaging of Cellular Inflammatory Response in Granuloma Formation Using Fluorescence-Labeled Macrophages

Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

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