Linjie Bian,Panli Li,Yigang Chen,Simin He,Jianping Zhang,Xiaoping Xu,Jindian Li,Shaoli Song
{"title":"Uridine-Based PET/NIRF Dual-Modality imaging for precision tumor diagnosis and surgery.","authors":"Linjie Bian,Panli Li,Yigang Chen,Simin He,Jianping Zhang,Xiaoping Xu,Jindian Li,Shaoli Song","doi":"10.1007/s00259-025-07573-9","DOIUrl":null,"url":null,"abstract":"PURPOSE\r\nMetabolic 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.\r\n\r\nMETHODS\r\nWe 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.\r\n\r\nRESULTS\r\n[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.\r\n\r\nCONCLUSION\r\nThis 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.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"13 1","pages":""},"PeriodicalIF":7.6000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-025-07573-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.