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

Abstract

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.