Quantifying receptor density in vivo using a dual-probe approach with fluorescence molecular imaging

Area of Science:

• Molecular imaging
• Optical imaging techniques
• Preclinical pharmaceutical testing

Background:

• Optical imaging is crucial for preclinical pharmaceutical testing but often lacks quantification of imaging probe reporters.
• Quantifying reporter expression is essential for accurate assessment of molecular targets.

Purpose of the Study:

• To develop and validate a novel dual-probe fluorescence imaging method for quantifying endothelial growth factor receptor (EGFR) expression.
• To assess the feasibility of this method in both simulated and in vivo preclinical models.

Main Methods:

• Dual-probe fluorescence imaging using a targeted EGFR probe and a non-targeted probe.
• Tracer kinetic compartmental modeling to analyze probe uptake curves.
• Application in simulation experiments and an in vivo mouse study across various tissue types (pancreas, pancreas tumor, leg).

Main Results:

• The novel method successfully quantified EGFR expression in simulated and in vivo models.
• Binding potentials for EGFR were 8.57 (pancreas), 25.64 (pancreas tumor), and 0.11 (leg).
• Results correlated with expected EGFR expression levels, showing higher expression in the pancreas than the leg, and significantly higher in the tumor compared to healthy tissues.

Conclusions:

• Dual-probe fluorescence imaging combined with tracer kinetic modeling provides a robust method for quantifying target expression.
• This approach enhances the utility of optical imaging in preclinical pharmaceutical research.
• Accurate quantification of EGFR expression is achievable and valuable for drug development and biomarker studies.