基于尿嘧啶的PET/NIRF双模成像用于肿瘤的精确诊断和手术。

IF 7.6 1区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Linjie Bian,Panli Li,Yigang Chen,Simin He,Jianping Zhang,Xiaoping Xu,Jindian Li,Shaoli Song
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引用次数: 0

摘要

目的:代谢重编程允许癌细胞在营养匮乏的条件下存活和增殖。尿苷是嘧啶代谢的中心分子,支持核苷酸生物合成和氧化还原稳态。然而,平衡核苷转运蛋白1 (ENT1)介导的尿苷转运缺乏高灵敏度成像工具,限制了在精确诊断和术中指导中的应用。本研究旨在开发和验证一种针对ent1介导的尿苷转运的新型双模成像平台,用于肿瘤成像和手术导航。方法合成[68Ga]Ga-DOTA-FZUD和ICG-FZUD探针,分别用于PET和NIR-II荧光成像。进行小动物PET/CT和NIR-II荧光成像,分析生物分布。采用ICG-FZUD对3例胃癌患者手术标本进行体外NIR-II荧光成像,确认肿瘤靶向性。结果[68Ga]Ga-DOTA-FZUD具有优异的放射化学纯度。在ENT1表达较高的胰腺癌模型(AsPC-1, Panc-1)中,与ENT1表达较低的模型(MiaPaCa-2, BxPC-3)相比,[68Ga]Ga-DOTA-FZUD显示出更大的肿瘤摄取。在胃、乳腺和胶质母细胞瘤模型中也观察到类似的摄取,肿瘤与肌肉的比例一直超过3.5。ICG-FZUD可实现高对比度NIR-II成像,清晰描绘肿瘤边缘。值得注意的是,ICG-FZUD穿透血脑屏障,显示原位胶质母细胞瘤。人胃癌组织的离体成像证实了选择性肿瘤摄取,与组织病理学结果一致。结论以ent1为靶点的尿苷转运PET/NIRF双模成像平台补充了传统的基于葡萄糖的成像,并提供了术中实时导航。它对早期癌症诊断和精确手术具有重要的前景,具有强大的转化潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Uridine-Based PET/NIRF Dual-Modality imaging for precision tumor diagnosis and surgery.
PURPOSE Metabolic reprogramming allows cancer cells to survive and proliferate under nutrient-deprived conditions. Uridine, a central molecule in pyrimidine metabolism, supports both nucleotide biosynthesis and redox homeostasis. However, high-sensitivity imaging tools for equilibrative nucleoside transporter 1 (ENT1)-mediated uridine transport are lacking, limiting applications in precise diagnosis and intraoperative guidance. This study aimed to develop and validate a novel dual-modality imaging platform targeting ENT1-mediated uridine transport for tumor imaging and surgical navigation. METHODS We synthesized [68Ga]Ga-DOTA-FZUD and ICG-FZUD probes for PET and NIR-II fluorescence imaging, respectively. Small-animal PET/CT and NIR-II fluorescence imaging were performed, and biodistribution were analyzed. Ex vivo NIR-II fluorescence imaging using ICG-FZUD was performed on surgical specimens from three gastric cancer patients to confirm tumor targeting. RESULTS [68Ga]Ga-DOTA-FZUD exhibited excellent radiochemical purity. In pancreatic cancer models with relatively higher ENT1 expression (AsPC-1, Panc-1) compared with lower ENT1 expression models (MiaPaCa-2, BxPC-3), [68Ga]Ga-DOTA-FZUD demonstrated markedly greater tumor uptake. Similar uptake was also observed in gastric, breast, and glioblastoma models, with tumor-to-muscle ratios consistently exceeding 3.5. ICG-FZUD enabled high-contrast NIR-II imaging and clearly delineated tumor margins. Notably, ICG-FZUD penetrated the blood-brain barrier and visualized orthotopic glioblastoma. Ex vivo imaging of human gastric cancer tissues confirmed selective tumor uptake, consistent with histopathological findings. CONCLUSION This ENT1-targeted uridine transport PET/NIRF dual-modality imaging platform complements conventional glucose-based imaging and provides real-time intraoperative navigation. It holds significant promise for early cancer diagnosis and precision surgery with strong translational potential.
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来源期刊
CiteScore
15.60
自引率
9.90%
发文量
392
审稿时长
3 months
期刊介绍: The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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