Whole-body tracking of single cells via positron emission tomography

Jung, Kyung Oh; Kim, Tae Jin; Yu, Jung Ho; Rhee, Siyeon; Zhao, Wei; Ha, Byung Hang; Red-Horse, Kristy; Gambhir, Sanjiv S.; Pratx, Guillem

doi:10.1038/s41551-020-0570-5

Cited by 53 publications

(89 citation statements)

References 36 publications

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“…Therefore, cellular activities need to be examined after radiolabeling. In the present study, the cell viability was almost unaffected by 64 Cu metabolic radiolabeling for up to 24 h, and after 48 h the labeled CTLs exhibited less DNA damage than CTLs exposed to X-ray radiation, which is comparable to the results recently reported using 68 Ga-mesoporous silica nanoparticle cell-labeling strategy [ 37 ]. Moreover, our labeling method did not affect the function of the CTLs, as determined using an enzyme-linked immunosorbent assay (ELISA) of IFN-γ.…”

Section: Discussionsupporting

confidence: 90%

“…Other ex vivo methods for T cell labeling reported previously include the use of 111 In-oxine [ 32 ] or 89 Zr-oxine [ 33 , 34 ], the use of 64 Cu-PTSM [ 35 ], and the treatment of the TCR-specific monoclonal antibody KJ1-26 with radionuclides to label cells via endocytosis [ 36 ]. Most recently, mesoporous silica nanoparticles containing 68 Ga or 89 Zr have also been used to label cells, enabling the tracking of individual cells using high-resolution PET imaging [ 37 ]. Although it is a straightforward approach, ex vivo labeling of T cells may cause cell toxicity because T cells are sensitive to radiation [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the glycan engineering method used in the present study resulted in favorable retention of radionuclide on the cell surface (88.42 ± 9.15% and 81.31 ± 6.40% for 24 and 48 h, respectively; Fig. 3 d), which is markedly higher than that of the mesoporous silica nanoparticle method (less than 60% at 24 h) [ 37 ]. The high retention of radionuclide on the cell surface guaranteed the accurate detection of cells in vivo by PET imaging.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

Wang

Zhang

et al. 2021

J Nanobiotechnol

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Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

Wang

Zhang

et al. 2021

J Nanobiotechnol

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“…Positron-emitting isotopes commonly used include fluorine-18 ( 18 F), zirconium-89 ( 89 Zr), gallium-68 ( 68 Ga) [31] and copper-64 ( 64 Cu). Although no cell tracking techniques reliant on direct labeling and PET imaging are routinely used in the clinic, a couple of direct labeling options exist, including fluorodeoxyglucose ([ 18 F]FDG) and 89 Zr-oxine.…”

Section: Positron Emission Tomography: Fluorodeoxyglucose and Zirconiummentioning

confidence: 99%

Options for imaging cellular therapeutics in vivo: a multi-stakeholder perspective

et al. 2021

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Cell-based therapies have been making great advances toward clinical reality. Despite the increase in trial activity, few therapies have successfully navigated late-phase clinical trials and received market authorization. One possible explanation for this is that additional tools and technologies to enable their development have only recently become available. To support the safety evaluation of cell therapies, the Health and Environmental Sciences Institute Cell Therapy-Tracking, Circulation and Safety Committee, a multisector collaborative committee, polled the attendees of the 2017 International Society for Cell & Gene Therapy conference in London, UK, to understand the gaps and needs that cell therapy developers have encountered regarding safety evaluations in vivo. The goal of the survey was to collect information to inform stakeholders of areas of interest that can help ensure the safe use of cellular therapeutics in the clinic. This review is a response to the cellular imaging interests of those respondents. The authors offer a brief overview of available technologies and then highlight the areas of interest from the survey by describing how imaging technologies can meet those needs. The areas of interest include imaging of cells over time, sensitivity of imaging modalities, ability to quantify cells, imaging cellular survival and differentiation and safety concerns around adding imaging agents to cellular therapy protocols. The Health and Environmental Sciences Institute Cell Therapy-Tracking, Circulation and Safety Committee believes that the ability to understand therapeutic cell fate is vital for determining and understanding cell therapy efficacy and safety and offers this review to aid in those needs. An aim of this article is to share the available imaging technologies with the cell therapy community to demonstrate how these technologies can accomplish unmet needs throughout the translational process and strengthen the understanding of cellular therapeutics.

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“…Positron Emission Tomography (PET) as a functional imaging method, together with targeting radiotracers, has been widely used in clinical due to its precision and ultrahigh sensitivity 6 . To date, PET/CT and PET/MRI fusing imaging as novel multimodality technology combining bene ts of anatomic information from CT or MRI scan imaging and functional information from PET, have become one of the most powerful imaging methods in disease diagnosis and single cell tracking 7,8 .…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Comparative Study of a Novel 68 Ga-Labeled PSMA-Targeted Inhibitor and 68 Ga -PSMA-11

Chen

Cai

Feng

et al. 2021

Preprint

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68Ga-radiolabeled small molecules that specifically target prostate specific membrane antigen (PSMA) has been extensively investigated, and some of those tracers have been used in diagnosis of prostate cancer with 68Ga-positron emission tomography (68Ga-PET). Nevertheless, current 68Ga-labeled radiotracers show fair detection rates to metastasized prostate cancer lesions, especially to those with lower level of prostate specific antigen (PSA), which often occur in biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer 68Ga-SC691 with high affinity to prostate cancer cells and excellent pharmacokinetics. To this end, structural optimum was made on the bifunctional group, target motif, and linker while high affinity targeting scaffold was remained. In order to explore its potential in clinical, a comparative study was further performed in vitro and in vivo between 68Ga-SC691 and 68Ga-PSMA-11, the clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68Ga-SC691 had a favorable biodistribution property and can specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable uptake at LNCaP xenografts if not higher than 68Ga-PSMA-11.

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Whole-body tracking of single cells via positron emission tomography

Cited by 53 publications

References 36 publications

Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

Options for imaging cellular therapeutics in vivo: a multi-stakeholder perspective

In Vitro and in Vivo Comparative Study of a Novel 68 Ga-Labeled PSMA-Targeted Inhibitor and 68 Ga -PSMA-11

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