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

High Resolution Image Download MS PowerPoint Slide 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 89 Zr 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.