Feasibility of in vivo CAR T cells tracking using streptavidin–biotin-paired positron emission tomography,European Journal of Nuclear Medicine and Molecular Imaging

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Feasibility of in vivo CAR T cells tracking using streptavidin–biotin-paired positron emission tomography
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2022-07-29 , DOI: 10.1007/s00259-022-05923-5
Donghui Pan ₁ , Yan Wang _{2,

3} , Nan Xu ₄ , Yuping Xu ₁ , Xinyu Wang ₁ , Lizhen Wang ₁ , Junjie Yan ₁ , Lei Yu ₄ , Liyan Miao _{2,

3} , Guangji Wang ₅ , Min Yang ₁

Affiliation

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.

中文翻译：

使用链霉亲和素-生物素配对正电子发射断层扫描进行体内 CAR T 细胞追踪的可行性

背景

构建了一种新型报告系统，链霉亲和素 (SA)- [ ⁶⁸ Ga]Ga 标记的生物素（[ ⁶⁸ Ga]Ga-DOTA-生物素），并在本研究中评估了其对 CAR T 细胞行为进行 PET 成像的能力.

方法

测定了 SA 转导的抗 CD19-CAR T（表示为 SA-CD19-CAR T）细胞的体外活性和细胞毒性。^{首次在实体瘤模型中研究了使用 [ 68} Ga]Ga-DOTA-生物素监测 SA-CD19-CAR T 细胞增殖概况的可行性。^{此外，通过生物发光成像和 [ 68} Ga]Ga-DOTA-生物素 PET 成像同时评估 CAR T 细胞在全身血液肿瘤中的药效学和药代动力学。

结果

用 SA 转导后，修饰的 CAR T 细胞的活性和细胞毒性不受影响。PET 图像显示， CD19 ^{+ K562 实体瘤中 [}⁶⁸ Ga]Ga-DOTA-生物素的摄取在 SA-给药后 30 分钟和 96 小时分别为 0.67 ± 0.32 ID%/g 和 1.26 ± 0.13 ID%/g分别为CD19-CAR T细胞。证实SA-CD19-CAR T细胞可有效抑制Raji血液肿瘤的生长。然而，在 Raji 模型中检测到与 CD19-CAR T 细胞增殖相关的低放射性。