{"id":"doi:10.1371/journal.pone.0223814","kind":"article","title":"Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging","authors":["Lee SH","Soh H","Chung JH","Cho EH","Lee SJ","Ju JM","Sheen JH","Kim H","Oh SJ","Chung J","Choi K","Kim SY","Ryu JS"],"author_count":13,"year":2020,"published":"2020-01-07","venue":"PloS one","cited_by":39,"doi":"10.1371/journal.pone.0223814","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1371/journal.pone.0223814","archive_url":"https://space-kitty.com/papers/doi:10.1371/journal.pone.0223814","updated":null,"pmid":"31910217","pmcid":"PMC6946129","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6946129/pdf","abstract":"Introduction Chimeric antigen receptor (CAR) T-cells have been recently developed and are producing impressive outcomes in patients with hematologic malignancies. However, there is no standardized method for cell trafficking and in vivo CAR T-cell monitoring. We assessed the feasibility of real-time in vivo 89Zr-p-Isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS, DFO) labeled CAR T-cell trafficking using positron emission tomography (PET). Results The 89Zr-DFO radiolabeling efficiency of Jurkat/CAR and human peripheral blood mononuclear cells (hPBMC)/CAR T-cells was 70%-79%, and cell radiolabeling activity was 98.1-103.6 kBq/106 cells. Cell viability after radiolabeling was >95%. Cell proliferation was not significantly different during the early period after radiolabeling, compared with unlabeled cells; however, the proliferative capacity decreased over time (day 7 after labeling). IL-2 or IFN-γ secretion was not significantly different between unlabeled and labeled CAR T-cells. PET/magnetic resonance imaging in the xenograft model showed that most of the 89Zr-DFO-labeled Jurkat/CAR T-cells were distributed in the lung (24.4% ± 3.4%ID) and liver (22.9% ± 5.6%ID) by one hour after injection. The cells gradually migrated from the lung to the liver and spleen by day 1, and remained stable in these sites until day 7 (on day 7: lung 3.9% ± 0.3%ID, liver 36.4% ± 2.7%ID, spleen 1.4% ± 0.3%ID). No significant accumulation of labeled cells was identified in tumors. A similar pattern was observed in ex vivo biodistributions on day 7 (lung 3.0% ± 1.0%ID, liver 19.8% ± 2.2%ID, spleen 2.3% ± 1.7%ID). 89Zr-DFO-labeled hPBMC/CAR T-cells showed a similar distribution, compared with Jurkat/CAR T-cells, on serial PET images. CAR T cell distribution was cross-confirmed by flow cytometry, Alu polymerase chain reaction, and immunohistochemistry. Conclusion Real-time in vivo cell trafficking is feasible using PET imaging of 89Zr-DFO-labeled CAR T-cells. This can be used to investigate cellular kinetics, initial in vivo biodistribution, and safety profiles in future CAR T-cell development.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging\" by Lee SH, Soh H, Chung JH et al., https://doi.org/10.1371/journal.pone.0223814, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}