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Published on: October 27, 2023
Examining the Feasibility of Quantifying Receptor Availability Using Cross-Modality Paired-Agent Imaging
Boyu Meng1, Negar Sadeghipour2, Margaret R Folaron1
1Thayer School of Engineering, Dartmouth College, 03755, Hanover, NH, USA.
Purpose:
The ability to noninvasively quantify receptor availability (RA) in solid tumors is an aspirational goal of molecular imaging, often challenged by the influence of non-specific accumulation of the contrast agent. Paired-agent imaging (PAI) techniques aim to compensate for this effect by imaging the kinetics of a targeted agent and an untargeted isotype, often simultaneously, and comparing the kinetics of the two agents to estimate RA. This is usually accomplished using two spectrally distinct fluorescent agents, limiting the technique to superficial tissues and/or preclinical applications. Applying the approach in humans using conventional imaging modalities is generally infeasible since most modalities are unable to routinely image multiple agents simultaneously. We examine the ability of PAI to be implemented in a cross-modality paradigm, in which the targeted and untargeted agent kinetics are imaged with different modalities and used to recover receptor availability.
Procedures:
Eighteen mice bearing orthotopic brain tumors were administered a solution containing three contrast agents: (1) a fluorescent agent targeted to epidermal growth factor receptor (EGFR), (2) an untargeted fluorescent isotype, and (3) a gadolinium-based contrast agent (GBCA) for MRI imaging. The kinetics of all three agents were imaged for 1 h after administration using an MRI-coupled fluorescence tomography system. Paired-agent receptor availability was computed using (1) the conventional all-optical approach using the targeted and untargeted optical agent images and (2) the cross-modality approach using the targeted optical and untargeted MRI-GBCA images. Receptor availability estimates between the two methods were compared.
Results:
Receptor availability values using the cross-modality approach were highly correlated to the conventional, single-modality approach (r = 0.94; p < 0.00001).
Conclusion:
These results suggest that cross-modality paired-agent imaging for quantifying receptor availability is feasible. Ultimately, cross-modality paired-agent imaging could facilitate rapid, noninvasive receptor availability quantification in humans using hybrid clinical imaging modalities.
Insights
Cross-modality paired-agent imaging (PAI) enables noninvasive quantification of receptor availability (RA) in tumors. This novel approach combines different imaging modalities to accurately estimate RA, overcoming limitations of traditional PAI techniques.
Area of Science:
- Molecular imaging
- Biophysics
- Radiochemistry
Background:
- Noninvasive quantification of receptor availability (RA) in solid tumors is crucial for molecular imaging.
- Traditional paired-agent imaging (PAI) techniques use spectrally distinct fluorescent agents, limiting applications to superficial tissues and preclinical studies.
- Simultaneous imaging of multiple agents is challenging with conventional clinical modalities.
Purpose of the Study:
- To investigate the feasibility of implementing PAI in a cross-modality paradigm.
- To assess the ability of cross-modality PAI to accurately quantify receptor availability.
- To overcome the limitations of single-modality PAI for human applications.
Main Methods:
- Eighteen mice with orthotopic brain tumors were used.
- Contrast agents included a targeted fluorescent agent (EGFR), an untargeted fluorescent agent, and a gadolinium-based contrast agent (GBCA) for MRI.
- Kinetics were imaged using an MRI-coupled fluorescence tomography system; RA was computed using both conventional all-optical PAI and cross-modality PAI (targeted optical + untargeted MRI-GBCA).
Main Results:
- Cross-modality PAI yielded receptor availability estimates highly correlated with the conventional single-modality approach (r = 0.94; p < 0.00001).
- This demonstrates strong agreement between the two PAI methods.
Conclusions:
- Cross-modality paired-agent imaging is a feasible approach for quantifying receptor availability.
- This technique has the potential to facilitate rapid, noninvasive RA quantification in humans.
- Hybrid clinical imaging modalities could enable widespread application of this cross-modality PAI method.
