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Published on: April 29, 2017
Biocompatible Glycoconjugation Enables Sensitive In Vivo Cell Tracking by PET/CT
Nathan Clemons1, Anna S Thickens1, Liudmila Lambert Lepesevich1
1Departments of Medical Physics and Radiology, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, Wisconsin 53705, United States.
Abstract:
Cell-based therapies have transformed the treatment landscape for cancer, yet their clinical translation remains limited by unpredictable in vivo behavior and variable patient responses. Accurate, noninvasive image-based tracking of therapeutic cells, such as PET/CT, is essential for understanding biodistribution, improving safety, and optimizing the design of next-generation treatments. However, existing radiolabeling strategies for cell tracking using PET/CT lack the stability and sensitivity required for reliable long-term imaging. Here, we present a direct radiolabeling strategy that oxidizes cell surface sialic acids to conjugate aminooxy-DFO (AOD) and subsequently radiolabels cells with 89Zr under biocompatible conditions. We radiolabeled five human and nonhuman primate immune cell types with high radiochemical incorporation (17-194 μCi per million cells) and purity (∼90%), while preserving cell viability. Serial PET/CT imaging over 7-8 days revealed conserved biodistribution patterns across all cell types tested. This approach provides a robust, applicable platform for longitudinal PET/CT tracking of therapeutic cells.
Insights
A new direct radiolabeling method enables stable, sensitive PET/CT imaging of therapeutic cells. This breakthrough improves tracking of cell biodistribution for enhanced cancer treatment safety and efficacy.
Area of Science:
- Biomedical Imaging
- Cellular Therapy
- Radiochemistry
Background:
- Cell-based cancer therapies show promise but face challenges in clinical translation due to unpredictable in vivo behavior.
- Noninvasive imaging techniques like PET/CT are crucial for tracking therapeutic cells, understanding biodistribution, and ensuring safety.
- Current PET/CT radiolabeling methods for cell tracking lack the necessary stability and sensitivity for long-term monitoring.
Purpose of the Study:
- To develop a direct, stable, and sensitive radiolabeling strategy for longitudinal PET/CT tracking of therapeutic cells.
- To evaluate the efficacy of the novel radiolabeling method across various immune cell types.
- To demonstrate the potential of this platform for optimizing next-generation cell therapies.
Main Methods:
- Developed a direct radiolabeling strategy by oxidizing cell surface sialic acids to conjugate aminooxy-DFO (AOD).
- Subsequently, cells were radiolabeled with 89Zr under biocompatible conditions.
- Five types of human and nonhuman primate immune cells were labeled and their viability assessed.
Main Results:
- Achieved high radiochemical incorporation (17-194 μCi/million cells) and purity (~90%) across all tested cell types.
- Cell viability was preserved post-radiolabeling.
- Serial PET/CT imaging over 7-8 days demonstrated conserved biodistribution patterns for all labeled cell types.
Conclusions:
- The direct radiolabeling strategy using AOD and 89Zr offers a robust and applicable platform for longitudinal PET/CT tracking of therapeutic cells.
- This method enhances the ability to monitor cell biodistribution, contributing to improved safety and efficacy of cell-based cancer therapies.
- The findings support the optimization of next-generation cell therapies through reliable in vivo cell tracking.
