Feasibility of in vivo CAR T cells tracking using streptavidin-biotin-paired positron emission tomography

作者：Pan, Donghui; Wang, Yan; Xu, Nan; Xu, Yuping; Wang, Xinyu; Wang, Lizhen; Yan, Junjie; Yu, Lei; Miao, Liyan^*; Wang, Guangji^*; Yang, Min^*

来源：European Journal of Nuclear Medicine and Molecular Imaging, 2022, 49(13): 4419-4426.

DOI：10.1007/s00259-022-05923-5

• CAR T cell
• Gallium-68
• Biotin
• Streptavidin
• PET

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.

• 单位
  1; 苏州大学