Donghui Pan1, Yan Wang2,3, Nan Xu4, Yuping Xu1, Xinyu Wang1, Lizhen Wang1, Junjie Yan1, Lei Yu4, Liyan Miao5,6, Guangji Wang7, Min Yang8. 1. NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China. 2. Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China. 3. Institute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215006, China. 4. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai UniCAR Therapy Bio-Medicine Technology Co., Ltd, Shanghai, 200062, China. 5. Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China. miaolysuzhou@163.com. 6. Institute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215006, China. miaolysuzhou@163.com. 7. Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China. gjwang@cpu.edu.cn. 8. NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China. yangmin@jsinm.org.
Abstract
BACKGROUND: A novel reporter system, streptavidin (SA)- [68 Ga]Ga-labeled biotin ([68 Ga]Ga-DOTA-biotin), was constructed and its ability for PET imaging the behaviors of CAR T cells were also evaluated in this study. METHODS: In vitro activity and cytotoxicity of the SA transduced anti-CD19-CAR T (denoted as SA-CD19-CAR T) cells were determined. The feasibility of monitoring proliferation profiles of SA-CD19-CAR T cells using [68 Ga]Ga-DOTA-biotin was firstly investigated in a solid tumor model. Also, the pharmacodynamics and pharmacokinetics of the CAR T cells in whole-body hematologic neoplasms were evaluated by bioluminescence imaging and [68 Ga]Ga-DOTA-biotin PET imaging simultaneously. RESULTS: After transduction with SA, the activity and cytotoxicity of the modified CAR T cells were not affected. PET images revealed that the uptakes of [68 Ga]Ga-DOTA-biotin in CD19+ K562 solid tumors were 0.67 ± 0.32 ID%/g and 1.26 ± 0.13 ID%/g at 30 min and 96 h p.i. after administration of SA-CD19-CAR T cells respectively. It confirmed that the SA-CD19-CAR T cells could effectively inhibit the growth of Raji hematologic tumors. However, low radioactivity related to the proliferation of CD19-CAR T cells was detected in the Raji model. CONCLUSION: SA-CD19-CAR T cells were constructed successfully without disturbing the antitumor functions of the cells. The proliferation of the CAR T cells in solid tumors could be early detected by [68 Ga]Ga-DOTA-biotin PET imaging.
BACKGROUND: A novel reporter system, streptavidin (SA)- [68 Ga]Ga-labeled biotin ([68 Ga]Ga-DOTA-biotin), was constructed and its ability for PET imaging the behaviors of CAR T cells were also evaluated in this study. METHODS: In vitro activity and cytotoxicity of the SA transduced anti-CD19-CAR T (denoted as SA-CD19-CAR T) cells were determined. The feasibility of monitoring proliferation profiles of SA-CD19-CAR T cells using [68 Ga]Ga-DOTA-biotin was firstly investigated in a solid tumor model. Also, the pharmacodynamics and pharmacokinetics of the CAR T cells in whole-body hematologic neoplasms were evaluated by bioluminescence imaging and [68 Ga]Ga-DOTA-biotin PET imaging simultaneously. RESULTS: After transduction with SA, the activity and cytotoxicity of the modified CAR T cells were not affected. PET images revealed that the uptakes of [68 Ga]Ga-DOTA-biotin in CD19+ K562 solid tumors were 0.67 ± 0.32 ID%/g and 1.26 ± 0.13 ID%/g at 30 min and 96 h p.i. after administration of SA-CD19-CAR T cells respectively. It confirmed that the SA-CD19-CAR T cells could effectively inhibit the growth of Raji hematologic tumors. However, low radioactivity related to the proliferation of CD19-CAR T cells was detected in the Raji model. CONCLUSION: SA-CD19-CAR T cells were constructed successfully without disturbing the antitumor functions of the cells. The proliferation of the CAR T cells in solid tumors could be early detected by [68 Ga]Ga-DOTA-biotin PET imaging.