한빛사논문
- 조회348
울산대학교 의과대학, 서울아산병원
Seog-Young Kim, Hyunsu Soh, Jin Hwa Jung, Eun Hye Cho, Hyori Kim, Ji-Min Ju, Joong Hyuk Sheen, Sang Ju Lee, Seung Jun Oh, Sang-Jin Lee, Junho Chung, Jin-Sook Ryu
From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic of Korea (J.M.J., J.H.S., Sang-Jin Lee); and Department of Biomedical Sciences, Seoul National University, Seoul, Republic of Korea (J.C.).
Address correspondence to J.S.R.
Abstract
Background
Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored.
Purpose
To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors.
Materials and Methods
CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells. After direct labeling with zirconium 89 (89Zr)-p-isothiocyanatobenzyl-desferrioxamine (DFO), CAR T cells were intravenously injected into immunodeficient mice with a CD19-positive and CD19-negative human tumor xenograft on the left and right flank, respectively. PET/MRI was used for direct in vivo imaging of 89Zr-DFO–labeled CAR T cells on days 0, 1, 3, and 7 and for indirect cell imaging with the radiolabeled somatostatin receptor-targeted ligand gallium 68 (68Ga)-DOTA-Tyr3-octreotide (DOTATOC) on days 6, 9, and 13. On day 13, mice were euthanized, and tissues and tumors were excised.
Results
The 89Zr-DFO–labeled CAR T cells were observed on PET/MRI scans in the liver and lungs of mice (n = 4) at all time points assessed. However, they were not visualized in CD19-positive or CD19-negative tumors, even on day 7. Serial 68Ga-DOTATOC PET/MRI showed CAR T cell accumulation in CD19-positive tumors but not in CD19-negative tumors from days 6 to 13. Notably, 68Ga-DOTATOC accumulation in CD19-positive tumors was highest on day 9 (mean percentage injected dose [%ID], 3.7% ± 1.0 [SD]) and decreased on day 13 (mean %ID, 2.6% ± 0.7) in parallel with a decrease in tumor volume (day 9: mean, 195 mm3 ± 27; day 13: mean, 127 mm3 ± 43) in the group with tumor growth inhibition. Enhanced immunohistochemistry staining of cluster of differentiation 3 (CD3) and hSSTr2 was also observed in excised CD19-positive tumor tissues.
Conclusion
Direct and indirect cell imaging with PET/MRI enabled in vivo tracking and monitoring of CAR T cells in an animal model.
논문정보
- Research article
- 2024년 02월 (BRIC 등록일 2024-02-29)
- 국내 연구진
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