Introduction: The gastrointestinal (GI) microbiota plays a pivotal role in various physiological processes. However, as microbial therapeutics evolve as treatments, optimizing delivery and understanding microbial dissemination and engraftment in vivo remain critical. We therefore developed a protocol for in vivo monitoring of microbial migration and GI permeability post-ingestion, using hybrid PET/MRI. Our objective was to radiolabel bacteria with 89Zr and use a porcine model to estimate organ-level dosimetry following ingestion. This research aims to pave the way for clinical investigations that track microbial therapies like FMT, probiotics and bacteriophage therapies.
Methods: We administered 89Zr-labeled Lactobacillus crispatus ATCC33820 or E. coli Nissle 1917 to 21 pigs. The pigs were longitudinally scanned between 0.5- and 7 days post-ingestion using a simultaneous 3T PET/MRI system (Siemens Biograph mMR). The mean net administered dose was 72.0 ± 15.0 MBq. During imaging acquisition, whole-body PET scans were acquired simultaneously with MRI. Images were processed using 3D-Slicer, first by co-registering PET with MRI and then segmenting the organs. Organ tissue activity was extracted over time using region of interest statistics.
Results: The PET biodistribution of labelled bacteria post-ingestion, primarily localized within the GI tract before descending through the rectum and excretion in feces. Notably, the highest mean ED for 89Zr-labeled L. crispatus and E. coli Nissle were exhibited in the distal and proximal colon. Conversely, ED estimates for the brain, lungs, heart, liver, kidney, small intestine, bladder and rectum remained low: < 5 µSv/MBq.
Discussion: In healthy pigs, 89Zr-L. crispatus and E. coli Nissle remained in the digestive tract until excretion. The whole-body ED for L. crispatus and E. coli Nissel and organ mean ED align with previously reported values for ingested tracers. We are pursuing regulatory approval to enable future clinical implementation of PET/MRI for tracking microbial therapies in humans.