Uridine-Based PET/NIRF Dual-Modality imaging for precision tumor diagnosis and surgery

Area of Science:

• Oncology
• Molecular Imaging
• Biochemistry

Background:

• Cancer cells exhibit metabolic reprogramming to survive nutrient deprivation.
• Uridine is crucial for pyrimidine metabolism, nucleotide synthesis, and redox balance.
• Lack of high-sensitivity imaging tools for equilibrative nucleoside transporter 1 (ENT1)-mediated uridine transport hinders precise cancer diagnosis and surgical guidance.

Purpose of the Study:

• To develop and validate a novel dual-modality imaging platform targeting ENT1-mediated uridine transport.
• To enable precise tumor imaging and intraoperative surgical navigation.

Main Methods:

• Synthesis of [⁶⁸Ga]Ga-DOTA-FZUD for PET and ICG-FZUD for NIR-II fluorescence imaging.
• Small-animal PET/CT and NIR-II fluorescence imaging in various cancer models.
• Ex vivo imaging of human gastric cancer surgical specimens to confirm tumor targeting.

Main Results:

• [⁶⁸Ga]Ga-DOTA-FZUD showed high tumor uptake in models with higher ENT1 expression across pancreatic, gastric, breast, and glioblastoma.
• ICG-FZUD provided high-contrast NIR-II imaging, clearly delineating tumor margins and penetrating the blood-brain barrier.
• Ex vivo analysis confirmed selective tumor uptake in human gastric cancer tissues, correlating with histopathology.

Conclusions:

• The ENT1-targeted uridine transport PET/NIRF dual-modality imaging platform offers an alternative to glucose-based imaging.
• This platform provides real-time intraoperative navigation capabilities.
• It shows significant promise for early cancer diagnosis, precision surgery, and has strong translational potential.