التفاصيل البيبلوغرافية
| العنوان: |
Feasibility of real-time in vivo89Zr-DFO-labeled CAR T-cell trafficking using PET imaging. |
| المؤلفون: |
Lee, Suk Hyun, Soh, Hyunsu, Chung, Jin Hwa, 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 |
| المصدر: |
PLoS ONE; 1/7/2020, Vol. 15 Issue 1, p1-21, 21p |
| مصطلحات موضوعية: |
POSITRON emission tomography, FLUORODEOXYGLUCOSE F18, CHIMERIC antigen receptors, BLOOD cells, MAGNETIC resonance imaging, POLYMERASE chain reaction |
| مستخلص: |
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 vivo89Zr-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 FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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