使用链霉亲和素-生物素配对正电子发射断层显像进行体内 CAR-T 细胞示踪的可行性

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.

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.

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.

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.