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Comparison of Kinetic Models for Dual-Tracer Receptor Concentration Imaging in Tumors
Nazanin Hamzei1, Kimberley S Samkoe2, Jonathan T Elliott3
1Biomedical Engineering Despartment, Illinois Institute of Technology, Chicago IL 60616, USA.
Abstract:
Molecular differences between cancerous and healthy tissue have become key targets for novel therapeutics specific to tumor receptors. However, cancer cell receptor expression can vary within and amongst different tumors, making strategies that can quantify receptor concentration in vivo critical for the progression of targeted therapies. Recently a dual-tracer imaging approach capable of providing quantitative measures of receptor concentration in vivo was developed. It relies on the simultaneous injection and imaging of receptor-targeted tracer and an untargeted tracer (to account for non-specific uptake of the targeted tracer). Early implementations of this approach have been structured on existing "reference tissue" imaging methods that have not been optimized for or validated in dual-tracer imaging. Using simulations and mouse tumor model experimental data, the salient findings in this study were that all widely used reference tissue kinetic models can be used for dual-tracer imaging, with the linearized simplified reference tissue model offering a good balance of accuracy and computational efficiency. Moreover, an alternate version of the full two-compartment reference tissue model can be employed accurately by assuming that the K1s of the targeted and untargeted tracers are similar to avoid assuming an instantaneous equilibrium between bound and free states (made by all other models).
Insights
This study validates reference tissue models for dual-tracer imaging, crucial for quantifying cancer receptor concentration in vivo. The linearized simplified reference tissue model provides an efficient and accurate method for targeted therapy development.
Area of Science:
- Nuclear medicine
- Molecular imaging
- Pharmacokinetics
Background:
- Targeted cancer therapies rely on understanding molecular differences between cancerous and healthy tissues.
- Quantifying tumor receptor expression in vivo is essential due to variations within and between tumors.
- Dual-tracer imaging offers a method to measure receptor concentration, accounting for non-specific tracer uptake.
Purpose of the Study:
- To evaluate the suitability of existing reference tissue kinetic models for dual-tracer imaging.
- To identify the most accurate and computationally efficient model for quantifying receptor concentration in vivo.
- To optimize dual-tracer imaging analysis for targeted therapy applications.
Main Methods:
- Simulations were performed to assess various reference tissue kinetic models.
- Experimental data from mouse tumor models were used for validation.
- The performance of different models was analyzed based on accuracy and computational efficiency.
Main Results:
- All commonly used reference tissue kinetic models are applicable to dual-tracer imaging.
- The linearized simplified reference tissue model demonstrated a favorable balance of accuracy and computational efficiency.
- An alternative two-compartment reference tissue model accurately quantified receptor concentration by assuming similar tracer influx rate constants (K1).
Conclusions:
- Reference tissue models are viable for dual-tracer imaging in quantitative oncology.
- The linearized simplified reference tissue model is recommended for its balance of performance.
- Optimized kinetic modeling enhances the precision of in vivo receptor quantification for targeted therapies.
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