Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging.
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...
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doaj-9cf50213746141779aec1f047a23be672021-03-03T21:19:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022381410.1371/journal.pone.0223814Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging.Suk Hyun LeeHyunsu SohJin Hwa ChungEun Hye ChoSang Ju LeeJi-Min JuJoong Hyuk SheenHyori KimSeung Jun OhSang-Jin LeeJunho ChungKyungho ChoiSeog-Young KimJin-Sook RyuINTRODUCTION: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.https://doi.org/10.1371/journal.pone.0223814 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Suk Hyun Lee Hyunsu Soh Jin Hwa Chung Eun Hye Cho Sang Ju Lee Ji-Min Ju Joong Hyuk Sheen Hyori Kim Seung Jun Oh Sang-Jin Lee Junho Chung Kyungho Choi Seog-Young Kim Jin-Sook Ryu |
spellingShingle |
Suk Hyun Lee Hyunsu Soh Jin Hwa Chung Eun Hye Cho Sang Ju Lee Ji-Min Ju Joong Hyuk Sheen Hyori Kim Seung Jun Oh Sang-Jin Lee Junho Chung Kyungho Choi Seog-Young Kim Jin-Sook Ryu Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. PLoS ONE |
author_facet |
Suk Hyun Lee Hyunsu Soh Jin Hwa Chung Eun Hye Cho Sang Ju Lee Ji-Min Ju Joong Hyuk Sheen Hyori Kim Seung Jun Oh Sang-Jin Lee Junho Chung Kyungho Choi Seog-Young Kim Jin-Sook Ryu |
author_sort |
Suk Hyun Lee |
title |
Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
title_short |
Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
title_full |
Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
title_fullStr |
Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
title_full_unstemmed |
Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
title_sort |
feasibility of real-time in vivo 89zr-dfo-labeled car t-cell trafficking using pet imaging. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0223814 |
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