Accounting for pharmacokinetic differences in dual-tracer receptor density imaging

Area of Science:

• Molecular imaging
• Biophysics
• Pharmacokinetics

Background:

• Dual-tracer molecular imaging quantifies receptor expression using targeted and untargeted tracers.
• Previous methods required identical pharmacokinetics for both tracers, limiting applicability.
• Epidermal growth factor receptor (EGFR) is overexpressed in many cancers.

Purpose of the Study:

• To develop and evaluate a novel methodology for dual-tracer molecular imaging.
• To correct for pharmacokinetic differences between targeted and untargeted tracers.
• To accurately quantify epidermal growth factor receptor (EGFR) expression in vivo.

Main Methods:

• Derived a deconvolution method to correct for differences in arterial input functions and binding-independent delivery/retention.
• Evaluated the methodology in a mouse U251 glioma xenograft model.
• Used fluorescently labeled, EGFR-targeted and untargeted Affibody tracers with known different blood clearance rates.

Main Results:

• Simulations showed that blood and vascular-permeability differences could be quantified via deconvolution.
• Without correction, dual-tracer modeling overestimated EGFR concentration (3.9 ± 2.4 nM vs. expected 2.0 ± 0.4 nM).
• Deconvolution correction yielded an accurate EGFR concentration of 2.0 ± 0.4 nM.

Conclusions:

• The developed deconvolution methodology effectively corrects for pharmacokinetic differences in dual-tracer molecular imaging.
• This approach enables more accurate quantification of receptor expression, such as EGFR, in cancer models.
• The findings advance the application of dual-tracer imaging for precise molecular diagnostics and therapeutics.