Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Tissue factor (TF) is upregulated in solid tumors, influencing angiogenesis, invasion, metastasis, and prognosis.
• Noninvasive assessment of tumor TF expression is clinically relevant for treatment strategies.
• Factor VII is the natural ligand for TF, making it a target for imaging.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) tracer for specific imaging of tumor TF expression.
• To assess the feasibility of using an (18)F-labeled derivative of factor VII for in vivo PET imaging.

Main Methods:

• Active site-inhibited factor VIIa (FVIIai) was radiolabeled with (18)F.
• The (18)F-FVIIai tracer was injected into nude mice bearing human pancreatic xenograft tumors.
• Small-animal PET/CT imaging, ex vivo biodistribution, and blocking experiments were performed.
• Tumor TF expression was validated using immunohistochemistry and ELISA.

Main Results:

• PET imaging demonstrated high uptake of (18)F-FVIIai in tumor regions (mean 2.5 ± 0.3 %ID/g at 4h), significantly higher than in muscle.
• Tumor uptake of (18)F-FVIIai showed a significant reduction (P < 0.001) in blocking experiments.
• In vivo PET imaging uptake of (18)F-FVIIai correlated significantly (r = 0.72, P < 0.02) with ex vivo measured TF protein levels.

Conclusions:

• (18)F-FVIIai is a promising PET tracer for specific and noninvasive imaging of tumor TF expression.
• The tracer demonstrates potential for clinical translation as a companion diagnostic for TF-targeted therapies.