7 Non-radioactive imaging strategies for in vivo immune cell tracking

Abstract In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.

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X-ray-Fluorescence Imaging for In Vivo Detection of Gold-Nanoparticle-Labeled Immune Cells: A GEANT4 Based Feasibility Study

Cancers ◽

10.3390/cancers13225759 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5759

Author(s):

Arthur Ungerer ◽

Theresa Staufer ◽

Oliver Schmutzler ◽

Christian Körnig ◽

Kai Rothkamm ◽

...

Keyword(s):

Fluorescence Imaging ◽

Cell Tracking ◽

Immune Cell ◽

High Sensitivity ◽

Diagnostic Tools ◽

Monte Carlo Simulation Study ◽

X Ray ◽

In Vivo Detection ◽

Technological Developments

The growing field of cellular therapies in regenerative medicine and oncology calls for more refined diagnostic tools that are able to investigate and monitor the function and success of said therapies. X-ray Fluorescence Imaging (XFI) can be applied for molecular imaging with nanoparticles, such as gold nanoparticles (GNPs), which can be used in immune cell tracking. We present a Monte Carlo simulation study on the sensitivity of detection and associated radiation dose estimations in an idealized setup of XFI in human-sized objects. Our findings demonstrate the practicability of XFI in human-sized objects, as immune cell tracking with a minimum detection limit of 4.4 × 105 cells or 0.86 μg gold in a cubic volume of 1.78 mm3 can be achieved. Therefore, our results show that the current technological developments form a good basis for high sensitivity XFI.

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Nuclear imaging for immune cell tracking in vivo – Comparison of various cell labeling methods and their application

Coordination Chemistry Reviews ◽

10.1016/j.ccr.2021.214008 ◽

2021 ◽

Vol 445 ◽

pp. 214008

Author(s):

Łukasz Kiraga ◽

Paulina Kucharzewska ◽

Stephen Paisey ◽

Łukasz Cheda ◽

Anita Domańska ◽

...

Keyword(s):

Cell Tracking ◽

Immune Cell ◽

Nuclear Imaging ◽

Cell Labeling

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In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Cancers ◽

10.3390/cancers13205069 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5069

Author(s):

Massis Krekorian ◽

Kimberley R. G. Cortenbach ◽

Milou Boswinkel ◽

Annemarie Kip ◽

Gerben M. Franssen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cell Tracking ◽

Immune Cell ◽

Specific Activity ◽

Ex Vivo ◽

Cell Labeling ◽

Aureus Infection ◽

Cell Based Therapy ◽

Number Of Cells

The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. 111In-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([111In]In-PLGA-NH2 NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed 89Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH2 NPs with [89Zr]ZrCl4. In vitro, [89Zr]Zr-PLGA-NH2 NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 ± 10 kBq/106 cells). PET/MRI imaging could detect low numbers of [89Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [89Zr]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular Staphylococcus aureus infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [89Zr]Zr-PLGA-NH2 NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models.

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Advances in Molecular Imaging Strategies forIn VivoTracking of Immune Cells

BioMed Research International ◽

10.1155/2016/1946585 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Ho Won Lee ◽

Prakash Gangadaran ◽

Senthilkumar Kalimuthu ◽

Byeong-Cheol Ahn

Keyword(s):

Computerized Tomography ◽

Immune Cells ◽

Cell Tracking ◽

Immune Cell ◽

Single Photon ◽

Imaging Techniques ◽

Photon Emission ◽

Nuclear Imaging ◽

Cell Based Therapy

Tracking of immune cellsin vivois a crucial tool for development and optimization of cell-based therapy. Techniques for tracking immune cells have been applied widely for understanding the intrinsic behavior of immune cells and include non-radiation-based techniques such as optical imaging and magnetic resonance imaging (MRI), radiation-based techniques such as computerized tomography (CT), and nuclear imaging including single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Each modality has its own strengths and limitations. To overcome the limitations of each modality, multimodal imaging techniques involving two or more imaging modalities are actively applied. Multimodal techniques allow integration of the strengths of individual modalities. In this review, we discuss the strengths and limitations of currently available preclinicalin vivoimmune cell tracking techniques and summarize the value of immune cell tracking in the development and optimization of immune cell therapy for various diseases.

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Natural Barcodes for Longitudinal Single Cell Tracking of Leukemic and Immune Cell Dynamics

Frontiers in Immunology ◽

10.3389/fimmu.2021.788891 ◽

2022 ◽

Vol 12 ◽

Author(s):

Livius Penter ◽

Satyen H. Gohil ◽

Catherine J. Wu

Keyword(s):

Single Cell ◽

Cell Tracking ◽

Immune Cell ◽

Single Cell Analysis ◽

Cell Populations ◽

Cellular Interactions ◽

Nucleotide Polymorphisms ◽

Hematopoietic Stem ◽

Disease Evolution

Blood malignancies provide unique opportunities for longitudinal tracking of disease evolution following therapeutic bottlenecks and for the monitoring of changes in anti-tumor immunity. The expanding development of multi-modal single-cell sequencing technologies affords newer platforms to elucidate the mechanisms underlying these processes at unprecedented resolution. Furthermore, the identification of molecular events that can serve as in-vivo barcodes now facilitate the tracking of the trajectories of malignant and of immune cell populations over time within primary human samples, as these permit unambiguous identification of the clonal lineage of cell populations within heterogeneous phenotypes. Here, we provide an overview of the potential for chromosomal copy number changes, somatic nuclear and mitochondrial DNA mutations, single nucleotide polymorphisms, and T and B cell receptor sequences to serve as personal natural barcodes and review technical implementations in single-cell analysis workflows. Applications of these methodologies include the study of acquired therapeutic resistance and the dissection of donor- and host cellular interactions in the context of allogeneic hematopoietic stem cell transplantation.

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Optical and genetic tools for in vivo single cell tracking

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2021.109192 ◽

2021 ◽

Vol 358 ◽

pp. 109192

Author(s):

Yajie Liang ◽

Liset M. de la Prida

Keyword(s):

Single Cell ◽

Cell Tracking ◽

Genetic Tools

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A Set of Cell Lines Derived from a Genetic Murine Glioblastoma Model Recapitulates Molecular and Morphological Characteristics of Human Tumors

Cancers ◽

10.3390/cancers13020230 ◽

2021 ◽

Vol 13 (2) ◽

pp. 230

Author(s):

Barbara Costa ◽

Michael N.C. Fletcher ◽

Pavle Boskovic ◽

Ekaterina L. Ivanova ◽

Tanja Eisemann ◽

...

Keyword(s):

Cell Lines ◽

Immune Cell ◽

Treatment Options ◽

Morphological Characteristics ◽

Molecular Heterogeneity ◽

Double Knockout ◽

In Vivo Models ◽

Human Glioblastoma ◽

Human Gbm

Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for deciphering glioma biology and for the development of effective treatment options. The murine GBM cell lines currently available for engraftment in immunocompetent mice are not only exiguous but also inadequate in representing prominent characteristics of human GBM such as infiltrative behavior, necrotic areas, and pronounced tumor heterogeneity. Therefore, we generated a set of glioblastoma cell lines by repeated in vivo passaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts, they formed high-grade gliomas that faithfully recapitulated the histopathological features, invasiveness and immune cell infiltration characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioblastoma pathomechanism and to test novel treatments in an intact immune microenvironment.

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An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

Communications Biology ◽

10.1038/s42003-021-02296-7 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Gheed Al-Hity ◽

FengWei Yang ◽

Eduard Campillo-Funollet ◽

Andrew E. Greenstein ◽

Hazel Hunt ◽

...

Keyword(s):

Immune System ◽

Immune Cell ◽

In Vitro Models ◽

Proof Of Concept ◽

Culture Model ◽

Spheroid Growth ◽

Confocal Images ◽

Cancer Spheroids

AbstractInvestigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

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Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420974893 ◽

2020 ◽

Vol 34 ◽

pp. 205873842097489

Author(s):

Jiang Wang ◽

Bo Wang ◽

Xin Lv ◽

Yingjie Wang

Keyword(s):

Alveolar Bone ◽

Immune Cell ◽

Critical Role ◽

Therapeutic Drug ◽

Mice Model ◽

T Helper 17 ◽

Th17 Cell Differentiation ◽

Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

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