Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging...

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Ecto-5'-nucleotidase (CD73) is overexpressed in aggressive cancers like TNBC and pancreatic cancer.
• CD73 is a promising target for cancer immunotherapy and diagnostic imaging.
• Small-molecule CD73 inhibitors are in clinical trials for cancer treatment.

Purpose of the Study:

• To develop and evaluate fluorine-18 labeled CD73 inhibitors as PET tracers.
• To assess the potential of these tracers for non-invasive imaging of CD73 expression in cancer.
• To compare the efficacy of novel tracers with existing imaging agents like [18F]FDG.

Main Methods:

• Selection of two high-affinity CD73 inhibitors (K_i ≈ 1 nM) for radiolabeling.
• Synthesis and evaluation of fluorine-18 labeled tracers: [¹⁸F]PSB-19427 ([¹⁸F]1) and [¹⁸F]MRS-4648 ([¹⁸F]2).
• Ex vivo imaging of human breast cancer tissues and in vivo studies in tumor models.

Main Results:

• Both [¹⁸F]1 and [¹⁸F]2 demonstrated specific binding in ex vivo studies.
• [¹⁸F]1 exhibited superior performance in vivo due to a long elimination half-life and accumulation in TNBC and pancreatic tumors.
• [¹⁸F]1 showed improved visualization of TNBC compared to [¹⁸F]FDG, suggesting higher specificity and diagnostic accuracy.

Conclusions:

• [¹⁸F]1 is a highly promising PET tracer for non-invasive imaging of CD73 expression in various solid tumors.
• The tracer offers potential advantages over [¹⁸F]FDG for TNBC imaging.
• [¹⁸F]1 is suitable for broad applications in cancer diagnosis and personalized medicine.