Multimodal Mass Spectrometry Imaging with a Metal-Based Alignment Tool Enables Targeted Single-Cell Boronophenylalanine Uptake and Metabolic Profiling in Glioblastoma Tumors

作者：Hao Fang, Lingna Zheng, Jiale Tian, Bo Huang, Shanshan Liang, Zhenzhen Ma, Xu Wang, Tingfeng Zhang, Haodong Yao, Lina Zhao, Bing Wang, Liuxing Feng, Meng Wang, Weiyue Feng · 发表于：Analytical Chemistry · 年份：2025 · DOI：10.1021/acs.analchem.5c04402 · 被引用次数：2 · 研究领域：Boron Compounds in Chemistry、Mass Spectrometry Techniques and Applications、Ion-surface interactions and analysis

Mass spectrometry imaging (MSI) is central to spatial multiomics; however, integrating multimodal MSI techniques and achieving accurate image coregistration remain major challenges. Here, we present an integrated multimodal MSI platform empowered by a novel metal-based alignment tool (MAT) for accurate coregistration across multimodal MSI. This platform combines laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) for single-cell elemental and isotope-tagged protein imaging with desorption electrospray ionization mass spectrometry (DESI-MS) for spatial metabolomics. Using this approach, we study the spatial distribution and metabolic fate of boronophenylalanine (BPA), a clinical boron carrier used in boron neutron capture therapy (BNCT), in an orthotopic U251 glioblastoma mouse model. Our data reveal a dual transport mechanism for BPA across both the blood-brain and blood-cerebrospinal fluid barriers. We observe pronounced intratumoral heterogeneity in boron uptake, spanning over a 2500-fold range, and identify six molecularly distinct tumor subpopulations, with the highest boron accumulation in proliferative and invasive phenotypes. Renal spatial metabolomics further show BPA clearance and biotransformation into tyrosine, 3-(4-boronophenyl)-2-hydroxypropanoic acid (BHA), and 3-(4-boronophenyl)-2-oxopropanoic acid (BOA), following the cortex-medulla-pelvis excretion pathway. This multimodal approach advances precision BNCT evaluation and ...