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

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.