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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Assembly-formed bioorthogonal chimeric artificial receptors enable high-contrast fluorescence imaging of tumors
Jianli Zuo1, Yuxi Tan2, Zhaode Mu1
1Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing, China.
Abstract:
Conventional receptor-targeted fluorescent probes have shown promise in tumor imaging, yet achieving a high tumor-to-normal (T/N) tissue ratio in vivo remains challenging due to limited biomarker density on tumor cell membranes. Here, we present an in situ assembly strategy of bioorthogonal-functionalized chimeric artificial receptors (BCARs) that locally constructs BCARs on tumor surfaces, which amplify fluorescence signals and enable high-contrast imaging. Rapid, selective membrane engineering under physiological conditions increases effective receptor density, enhancing fluorophore binding and tumor visualization. Mechanistic studies reveal that BCARs exhibit exceptional membrane retention and spatial precision, sustaining signal amplification in heterogeneous tumor microenvironments. In air-pouch and orthotopic bladder cancer models, BCARs notably improve the T/N imaging ratio and tumor boundary delineation. Translational validation with surgical specimens from 14 patients with bladder cancer confirms clinical feasibility. This work establishes a versatile platform for on-site receptor reprogramming and signal amplification, offering a powerful tool for high-contrast tumor margin detection.
Insights
This study introduces a novel bioorthogonal-functionalized chimeric artificial receptor (BCAR) strategy for in situ tumor imaging. BCARs enhance fluorescence signals for high-contrast tumor visualization and margin detection, improving the tumor-to-normal tissue ratio.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Oncology
Background:
- Conventional tumor imaging probes face challenges in achieving high tumor-to-normal (T/N) ratios due to low biomarker density.
- Limited effective receptor density on tumor cell membranes hinders optimal fluorescence signal amplification.
Purpose of the Study:
- To develop an in situ assembly strategy for bioorthogonal-functionalized chimeric artificial receptors (BCARs) to enhance tumor imaging contrast.
- To improve tumor visualization and delineation by amplifying fluorescence signals directly on tumor surfaces.
Main Methods:
- Developed an in situ assembly strategy using bioorthogonal-functionalized chimeric artificial receptors (BCARs).
- Engineered cell membranes under physiological conditions to increase effective receptor density.
- Evaluated BCAR performance in air-pouch and orthotopic bladder cancer models.
- Validated clinical feasibility using surgical specimens from bladder cancer patients.
Main Results:
- BCARs demonstrated rapid, selective membrane engineering, increasing effective receptor density.
- Achieved significant amplification of fluorescence signals, leading to enhanced tumor visualization.
- BCARs showed exceptional membrane retention and spatial precision in heterogeneous tumor microenvironments.
- Improved T/N imaging ratio and tumor boundary delineation in preclinical models.
- Confirmed clinical feasibility for high-contrast tumor margin detection.
Conclusions:
- The in situ BCAR assembly strategy offers a versatile platform for on-site receptor reprogramming and signal amplification.
- This approach enables high-contrast tumor imaging and precise margin detection.
- BCARs represent a powerful tool for improving diagnostic accuracy in oncology.
