Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging

Abstract

This study aims to employ magnetic particle imaging (MPI) for in vivo tracking and quantitative assessment of targeting capability of CLDN18.2-specific CAR-T cells. CLDN18.2-targeted CAR-T cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic particle imaging (MPI), and with the near-infrared fluorescent dye DiR for fluorescence molecular imaging (FMI) before infusion. SPIONs-labeled and unlabeled CAR-T cells were administered intravenously to NOD/SCID mice bearing HGC27 xenograft tumors, either independently or in combination with anti-PD-L1 (aPD-L1) antibody (n = 3 for imaging and n = 5 for treatment). The FMI and MPI successfully monitored the dynamic migration and tumor targeting of CAR-T cells towards CLDN18.2-overexpressing tumors. On the fifth day post-infusion, the MPI signal of SPIONs-labeled CAR-T cells was significantly higher in the tumor than that of labeled normal T cells. MPI combined with FMI successfully monitored the targeting of CLDN18.2-specific CAR-T cells in gastric cancer, providing a potential framework for evaluating CAR-T therapy combined with aPD-L1 immunotherapy.