Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging


Autoři: Suk Hyun Lee aff001;  Hyunsu Soh aff003;  Jin Hwa Chung aff003;  Eun Hye Cho aff001;  Sang Ju Lee aff001;  Ji-Min Ju aff005;  Joong Hyuk Sheen aff005;  Hyori Kim aff004;  Seung Jun Oh aff001;  Sang-Jin Lee aff005;  Junho Chung aff006;  Kyungho Choi aff006;  Seog-Young Kim aff004;  Jin-Sook Ryu aff001
Působiště autorů: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea aff001;  Department of Radiology, Division of Nuclear Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea aff002;  Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea aff003;  Convergence Medicine Research Center, Asan Medical Center, Seoul, Republic of Korea aff004;  Research Institute, National Cancer Center, Gyeonggi-do, Republic of Korea aff005;  Department of Biomedical Sciences, Seoul National University, Seoul, Republic of Korea aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0223814

Souhrn

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.

Klíčová slova:

Basic cancer research – Cancer immunotherapy – Liver – Polymerase chain reaction – Positron emission tomography – Radioactivity – Spleen – T cells


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