A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking

Harmsen, Stefan; Medine, E. Ilker; Moroz, Maxim A.; Nurili, Fuad; Lobo, Jose; Dong, Yiyu; Turkekul, Mezruh; Pillarsetty, Naga Vara Kishore; Ting, Richard; Ponomarev, Vladimir; Akın, Oğuz; Aras, Ömer

doi:10.1016/j.biomaterials.2020.120630

Cited by 42 publications

(43 citation statements)

References 28 publications

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“…In vivo cell tracking has been performed previously, using different combinations of labeling methods and imaging modalities. − Here we used the human monocyte cell line THP-1, an intermediate phagocytic cell line. Monocyte cells are progenitor cells of macrophages, which respond to inflammation signals.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

et al. 2021

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With the advent of novel immunotherapies, interest in ex vivo autologous cell labeling for in vivo cell tracking has revived. However, current clinically available labeling strategies have several drawbacks, such as release of radiolabel over time and cytotoxicity. Poly(lactic- co -glycolic acid) nanoparticles (PLGA NPs) are clinically used biodegradable carriers of contrast agents, with high loading capacity for multimodal imaging agents. Here we show the development of PLGA-based NPs for ex vivo cell labeling and in vivo cell tracking with SPECT. We used primary amine-modified PLGA polymers (PLGA-NH 2 ) to construct NPs similar to unmodified PLGA NPs. PLGA-NH 2 NPs were efficiently radiolabeled without chelator and retained the radionuclide for 2 weeks. Monocyte-derived dendritic cells labeled with [ 111 In]In-PLGA-NH 2 showed higher specific activity than those labeled with [ 111 In]In-oxine, with no negative effect on cell viability. SPECT/CT imaging showed that radiolabeled THP-1 cells accumulated at the Staphylococcus aureus infection site in mice. In conclusion, PLGA-NH 2 NPs are able to retain 111 In, independent of chelator presence. Furthermore, [ 111 In]In-PLGA-NH 2 allows cell labeling with high specific activity and no loss of activity over prolonged time intervals. Finally, in vivo tracking of ex vivo labeled THP-1 cells was demonstrated in an infection model using SPECT/CT imaging.

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Section: Discussionmentioning

confidence: 99%

Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

et al. 2021

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“…31 The ex vivo labeling of cells with radionuclides for SPECT or PET typically involves their complexation to a lipophilic ligand to allow transport of the radioisotopes across the cell membrane. 38 Alternatively, strategies have been developed that allow the labeling of cell surface receptors using radiolabeled antibodies or the covalent binding of radioisotope complexes. [39][40][41] For example, Griessinger et al 39 developed an intracellular labeling approach in which TCR-specific 64 Cu-labeled monoclonal antibodies were applied as an alternative to the more conventional 64…”

Section: Keynote (Green) Tablementioning

confidence: 99%

“…Endocytic internalization of the 64 Cuantibody-TCR complex, together with the continuous recycling of TCR to the plasma membrane, allowed stable labeling of the T cells with minimized impact on T cell viability and functionality. 35,38 Nanoparticle-based cell tracers (such as MRI contrast agents, 19 F-tracers or radiolabeled gold nanoparticles) are traditionally delivered via endocytosis, entrapping the majority of the tracers in the endolysosomal compartments, which could lead to signal instability and increased toxicity. [42][43][44] For example, the endocytic uptake of the MRI-contrast agent gadolinium can lead to increased endosomal concentrations and to the subsequent quenching of the MRI signal.…”

Section: Keynote (Green) Tablementioning

confidence: 99%

“…42,45 One alternative approach is to attach nanoparticles to the T cell surface directly, for example via covalent coupling to exofacial functional groups, while avoiding subsequent endocytosis. [46][47][48][49][50] Harmsen and coworkers 38 recently reported on the modification of CAR-T cells with 89 Zrlabeled near-infrared (NIR) silica nanoparticles in the presence of heparin and protamine, two oppositely charged polymers that can self-assemble into nanocomplexes and which were shown to facilitate CAR-T cell interaction and labeling. These dual-mode PET/NIR nanoparticles were retained in the T cells for up to 1 week and enabled non-invasive CAR-T cell tracking in an ovarian peritoneal carcinomatosis model.…”

Section: Keynote (Green) Tablementioning

confidence: 99%

“…These dual-mode PET/NIR nanoparticles were retained in the T cells for up to 1 week and enabled non-invasive CAR-T cell tracking in an ovarian peritoneal carcinomatosis model. 38,51 In addition, membrane-permeabilization techniques can be utilized to deliver cell tracers directly into the cell cytosol. [52][53][54] These intracellular delivery methods transiently disrupt the cell membrane using a physical (thermal, electrical, or optical) stimulus or a chemical trigger (such as an oxidant or pore-forming agent).…”

Section: Keynote (Green) Tablementioning

confidence: 99%

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Non-invasive cell-tracking methods for adoptive T cell therapies

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Nuclear Imaging of CAR T Immunotherapy to Solid Tumors: In Terms of Biodistribution, Viability, and Cytotoxic Effect

et al. 2023

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Immunotherapy has become a mainstay of cancer therapy. Since chimeric antigen receptor (CAR) T immunotherapy achieves unprecedented success in curing hematological malignancies, the possibility of it revolutionizing the paradigm of solid tumors has aroused increasing attention. However, the restricted accessibility to tumor parenchyma, the immunosuppressive tumor microenvironment, and antigen heterogeneity of solid tumors make it difficult to replicate its success. Therefore, dynamic evaluation of CAR T cells’ tumor accessibility, intratumoral viability, and anti‐tumor cytotoxicity is necessary to facilitate its translation to solid tumors. Besides, real‐timely imaging above events in vivo can help evaluate therapeutic responses and optimize CAR T immunotherapy for solid tumors. Nuclear imaging, including positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) imaging, is frequently applied for evaluating adoptive cell therapies owing to its excellent sensitivity, high tissue penetration, and great translation potential. In addition, quantitative analysis can be performed in dynamic and noninvasive patterns. This review focuses on recent advances in PET/SPECT technologies and imaging probes in monitoring CAR T cells’ migration, viability, and cytotoxicity to solid tumors post‐administration. Prospects of what should be done in the next stage to promote CAR T therapy's application in solid tumors are also discussed.

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A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking

Cited by 42 publications

References 28 publications

Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

Non-invasive cell-tracking methods for adoptive T cell therapies

Nuclear Imaging of CAR T Immunotherapy to Solid Tumors: In Terms of Biodistribution, Viability, and Cytotoxic Effect

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