Biocompatible Glycoconjugation Enables Sensitive In Vivo Cell Tracking by PET/CT.

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.