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<p>Locoregional CAR-T delivery is increasingly explored for glioblastoma to improve intracranial tumor exposure; however, organ-level biodistribution kinetics after intracranial administration remain poorly quantified in vivo, limiting route-informed optimization and preclinical risk assessment. Here, we report a dual-modality cell labeling and tracking strategy based on indocyanine green–conjugated iron nanoparticles (ICG-NPs) for in vivo assessment of B7-H3-targeting CAR-T cell (TX103) biodistribution using second near-infrared window (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI). Using a heparin–protamine-assisted protocol, TX103 cells were labeled with high efficiency (83.1%) without detectable changes in viability, CAR expression, immunophenotype (including activation/exhaustion marker profile and CXCR3 expression), or cytotoxic function. In vitro imaging demonstrated a linear correlation between NIR-II fluorescence intensity and labeled cell numbers (<i>R</i><sup>2</sup> = 0.973, <i>p</i> &lt; 0.001), while MRI provided complementary anatomical context at higher cell densities. In an orthotopic glioma mouse model, longitudinal MRI and NIR-II imaging captured route-dependent differences in tumor-associated localization and whole-body biodistribution following intracerebroventricular and intravenous administration. Furthermore, organ-level NIR-II exposure showed a positive association with CD3⁺ T-cell density across organs (<i>R</i><sup>2</sup> = 0.552, <i>p</i> &lt; 0.001), supported by multi-organ pathological validation. Collectively, we establish a biocompatible dual-modality workflow that links intracranial anatomical localization with longitudinal whole-body biodistribution readouts for preclinical CAR-T tracking in solid tumor models.</p> Graphical abstract <p>Schematic of the ICG–iron nanoparticle (ICG-NP) labeling workflow for B7-H3–targeting CAR-T cells (TX103) and dual-modality in vivo tracking using MRI (tumor-associated localization) and NIR-II fluorescence imaging (whole-body biodistribution) in an orthotopic glioma model, with pathological validation.</p>

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Dual-modality imaging enables longitudinal biodistribution profiling of intracerebroventricular CAR-T therapy in orthotopic glioma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月2日

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  • Chunzhao Li,
  • Peng Zhang,
  • Xiaobin Zhao,
  • Rui Feng,
  • Na Xian,
  • Gangxiong Huang,
  • Wenju Jiang,
  • Zhenhua Hu,
  • Yang Zhang,
  • Nan Ji

摘要

Locoregional CAR-T delivery is increasingly explored for glioblastoma to improve intracranial tumor exposure; however, organ-level biodistribution kinetics after intracranial administration remain poorly quantified in vivo, limiting route-informed optimization and preclinical risk assessment. Here, we report a dual-modality cell labeling and tracking strategy based on indocyanine green–conjugated iron nanoparticles (ICG-NPs) for in vivo assessment of B7-H3-targeting CAR-T cell (TX103) biodistribution using second near-infrared window (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI). Using a heparin–protamine-assisted protocol, TX103 cells were labeled with high efficiency (83.1%) without detectable changes in viability, CAR expression, immunophenotype (including activation/exhaustion marker profile and CXCR3 expression), or cytotoxic function. In vitro imaging demonstrated a linear correlation between NIR-II fluorescence intensity and labeled cell numbers (R2 = 0.973, p < 0.001), while MRI provided complementary anatomical context at higher cell densities. In an orthotopic glioma mouse model, longitudinal MRI and NIR-II imaging captured route-dependent differences in tumor-associated localization and whole-body biodistribution following intracerebroventricular and intravenous administration. Furthermore, organ-level NIR-II exposure showed a positive association with CD3⁺ T-cell density across organs (R2 = 0.552, p < 0.001), supported by multi-organ pathological validation. Collectively, we establish a biocompatible dual-modality workflow that links intracranial anatomical localization with longitudinal whole-body biodistribution readouts for preclinical CAR-T tracking in solid tumor models.

Graphical abstract

Schematic of the ICG–iron nanoparticle (ICG-NP) labeling workflow for B7-H3–targeting CAR-T cells (TX103) and dual-modality in vivo tracking using MRI (tumor-associated localization) and NIR-II fluorescence imaging (whole-body biodistribution) in an orthotopic glioma model, with pathological validation.