Tracking a Radiolabelled Probiotic Following Oral Administration in Pigs Using PET/MRI: Whole-Body Imaging and ⁸⁹Zr Label Release from Nissle 1917
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In seven pigs given radiolabelled E. coli Nissle 1917 capsules, 89Zr activity stayed in the gut with negligible systemic absorption. Labelling and freeze-thaw encapsulation reduced bacterial viability, and 89Zr release was considerable.
The gut microbiome influences host health, yet no clinical tool can resolve the spatial and temporal fate of orally administered microbial therapeutics, such as probiotics, . This thesis tested whether orally administered radiolabelled probiotic bacteria can be tracked using hybrid PET/MRI in a large animal (pig) model. Nissle 1917 (EcN) was radiolabelled with ⁸⁹Zr-desferrioxamine (⁸⁹Zr-DFO), encapsulated following standard fecal microbiota transplantation (FMT) capsule preparation, and administered to seven female Duroc pigs, with serial whole-body PET/MRI performed across 15 sessions over seven days at St. Joseph’s Health Care London, Ontario. , radiolabelling and freeze-thaw encapsulation reduced bacterial viability. Considerable ⁸⁹Zr release was also observed. , ⁸⁹Zr activity remained confined to the gastrointestinal tract, with negligible systemic absorption, and fecal clearance of EcN, measured by quantitative PCR (qPCR), was faster than that of ⁸⁹Zr, consistent with this release. In the stomach, a novel MRI-guided segmentation approach was used to quantify radioactivity separately in gas, fluid and digesta compartments, showing radiolabel in both fluid and digesta, with a negative voxel-level PET–MRI correlation supporting a stronger association with digesta. To the best of my knowledge, this work also produced the first porcine large-intestine MRI segmentation atlas, including identification of key anatomical features. The findings establish interpretive boundaries for ⁸⁹Zr-DFO labelling and provide a foundation for future microbiota imaging studies with radiolabelled bacteria, including a method for quantifying PET radioactivity in different gut compartments. They also provide anatomical information to support future imaging studies in pigs.
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