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

Cancer Immunol Immunother. 2026 May 2;75(5):160. doi: 10.1007/s00262-026-04403-1.

Chunzhao Li ¹ ², Peng Zhang ¹ ², Xiaobin Zhao ³, Rui Feng ⁴ ⁵, Na Xian ⁴ ⁵, Gangxiong Huang ⁴ ⁵, Wenju Jiang ⁶, Zhenhua Hu ⁷ ⁸ ⁹, Yang Zhang ¹⁰ ¹¹, Nan Ji ¹² ¹³ ¹⁴

Affiliations

1 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, Beijing, 100070, China.
2 China National Clinical Research Center for Neurological Diseases, Beijing, China.
3 Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
4 Fuzhou Tcelltech Biological Science and Technology Inc., Fuzhou, China.
5 Institute of Immunotherapy, Fujian Medical University, Fuzhou, China.
6 Beijing Arion Cancer Center, Beijing, China.
7 CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China. [email protected].
8 School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China. [email protected].
9 National Key Laboratory of Kidney Diseases, Beijing, China. [email protected].
10 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, Beijing, 100070, China. [email protected].
11 China National Clinical Research Center for Neurological Diseases, Beijing, China. [email protected].
12 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, Beijing, 100070, China. [email protected].
13 China National Clinical Research Center for Neurological Diseases, Beijing, China. [email protected].
14 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China. [email protected].

PMID: 42068336 DOI: 10.1007/s00262-026-04403-1

Abstract

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.

Keywords

CAR-T; Cell tracking; Glioblastoma; MRI; NIR-II.

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