Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging

Lee, Suk Hyun; Soh, Hyunsu; Chung, Jin-Gyun; Cho, Eun Hye; Lee, Sang Ju; Ju, Ji Min; Sheen, Joong Hyuk; Kim, Hyori; Oh, Seung Jun; Lee, Sang Jin; Chung, Junho; Choi, Kyungho; Kim, Seog Young; Ryu, Jin Sook

doi:10.1371/journal.pone.0223814

Cited by 33 publications

(34 citation statements)

References 29 publications

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“…89 Zr's long half-life (78.4 h) makes this nuclide suitable for long-term in vivo tracking. PET scanning captured these cells as they migrated between lung, liver, and spleen (79).…”

Section: Positron Emission Tomographymentioning

confidence: 99%

The Chimeric Antigen Receptor Detection Toolkit

Huang

2020

Front. Immunol.

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Chimeric antigen receptor-T (CAR-T) cell therapy is a promising frontier of immunoengineering and cancer immunotherapy. Methods that detect, quantify, track, and visualize the CAR, have catalyzed the rapid advancement of CART cell therapy from preclinical models to clinical adoption. For instance, CAR-staining/labeling agents have enabled flow cytometry analysis, imaging applications, cell sorting, and high-dimensional clinical profiling. Molecular assays, such as quantitative polymerase chain reaction, integration site analysis, and RNA-sequencing, have characterized CAR transduction, expression, and in vivo CART cell expansion kinetics. In vitro visualization methods, including confocal and total internal reflection fluorescence microscopy, have captured the molecular details underlying CAR immunological synapse formation, signaling, and cytotoxicity. In vivo tracking methods, including two-photon microscopy, bioluminescence imaging, and positron emission tomography scanning, have monitored CART cell biodistribution across blood, tissue, and tumor. Here, we review the plethora of CAR detection methods, which can operate at the genomic, transcriptomic, proteomic, and organismal levels. For each method, we discuss: (1) what it measures; (2) how it works; (3) its scientific and clinical importance; (4) relevant examples of its use; (5) specific protocols for CAR detection; and (6) its strengths and weaknesses. Finally, we consider current scientific and clinical needs in order to provide future perspectives for improved CAR detection.

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“…89 Zr's long half-life (78.4 h) makes this nuclide suitable for long-term in vivo tracking. PET scanning captured these cells as they migrated between lung, liver, and spleen (79).…”

Section: Positron Emission Tomographymentioning

confidence: 99%

The Chimeric Antigen Receptor Detection Toolkit

Huang

2020

Front. Immunol.

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“…In vivo monitoring of CAR T cell therapy using molecular imaging is an area of intensive investigation. Several groups, including ours, have explored the utility of reporter genes (11)(12)(13)(14)(15) or ex vivo radiolabeling approaches (16)(17)(18) to allow tracking of CAR T cell therapies with PET. The use of immunoPET has several advantages over these approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the enormous potential of this indirect labeling approach, major limitations of this strategy are the requirement for the generation and approval of entirely new CAR T cells specifically designed to incorporate the imaging functionality and a significant risk of immunogenicity. To circumvent these limitations, an alternative approach tested has been the ex vivo labeling of CAR T cells with radioactive tracers prior to administration (16)(17)(18). This approach has the advantage of being applicable to any CAR T cells including the currently commercially available ones, but has several limitations, principally limited temporal resolution, a function of the radioactive decay of the label employed.…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Simonetta

Alam

Lohmeyer

et al. 2021

Clinical Cancer Research

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In vivo Imaging of Activated Chimeric Antigen Receptor T Cells. Conflict-of-interest disclosures SSG is the founder and equity holder of CellSight Inc. that develops and translates strategies for imaging cell trafficking/transplantation. CLM holds several patent applications in the area of CAR T cell immunotherapy, is a founder of, holds equity in, and receives consulting fees from Lyell Immunopharma, has received consulting fees from NeoImmune Tech, Nektar Therapeutics and Apricity Health and royalties from Juno Therapeutics for the CD22-CAR. All other authors have declared that no conflict of interest exists. Significance ICOS-immunoPET enables in vivo imaging of activated CAR T cells at the tumor site without the need for incorporation of reporter transgenes or ex vivo biolabeling. Research.

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“…In contrast to the cell-permeable 89 Zr-oxine, 89 Zr-deferoxamine-NCS has been reported to directly conjugate 89 Zr to cell surface proteins for cell tracking by PET 53 , 54 . In this method, deferoxamine chelates 89 Zr, while the NCS group covalently binds primary amine groups of membrane proteins on the cell surface.…”

Section: Labeling Of Cells With 89 Zr-oxine For Pementioning

confidence: 99%

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

Kurebayashi¹,

Choyke²,

Sato³

2021

Nanotheranostics

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With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89 Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with 89 Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89 Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89 Zr-oxine PET-based imaging of cell-based therapy.

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Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging

Abstract: Introduction

Cited by 33 publications

References 29 publications

The Chimeric Antigen Receptor Detection Toolkit

The Chimeric Antigen Receptor Detection Toolkit

Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

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Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging

Abstract: Introduction

Cited by 33 publications

References 29 publications

The Chimeric Antigen Receptor Detection Toolkit

The Chimeric Antigen Receptor Detection Toolkit

Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography

Contact Info

Product

Resources

About

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography