Praveen Dassanayake, Diksha Diksha, Gabriel Varela-Mattatall, Qin Sun, Sarah C. Donnelly, Mojmir Suchy, Dianne Bartolome, Shaena Furlong, Lela Deans, Heather Biernaski, Yvonne Huston, R. Terry Thompson, Jeremy P. Burton, Gerald Moran, Neil Gelman, Frank S. Prato, Mike S. Kovacs, Jonathan D. Thiessen, Donna E. Goldhawk, James Schellenberg, Matthew S. Fox
{"title":"89锆标记菌群在猪肠道内的生物分布及剂量学研究","authors":"Praveen Dassanayake, Diksha Diksha, Gabriel Varela-Mattatall, Qin Sun, Sarah C. Donnelly, Mojmir Suchy, Dianne Bartolome, Shaena Furlong, Lela Deans, Heather Biernaski, Yvonne Huston, R. Terry Thompson, Jeremy P. Burton, Gerald Moran, Neil Gelman, Frank S. Prato, Mike S. Kovacs, Jonathan D. Thiessen, Donna E. Goldhawk, James Schellenberg, Matthew S. Fox","doi":"10.1002/mp.18087","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as <i>Escherichia coli</i> Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.</p>\n </section>\n \n <section>\n \n <h3> Purpose</h3>\n \n <p>We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with <sup>89</sup>Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We administered <sup>89</sup>Zr-labeled <i>Lactobacillus crispatus</i> ATCC33820 (Gram-positive) to six female Duroc pigs (weight = 33.3 ± 4.6 kg) and <i>E. coli</i> Nissle 1917 (Gram-negative). Scans were performed between 6 h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7 ± 12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T<sub>2</sub>-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>PET imaging showed <sup>89</sup>Zr-labeled <i>L. crispatus</i> and <i>E. coli</i> post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for <sup>89</sup>Zr-labeled <i>L. crispatus</i> and <i>E. coli</i> were in the distal colon (26.8 ± 4.9 µSv/MBq and 28.4 ± 7.9 µSv/MBq, respectively) and proximal colon (17.9 ± 3.7 µSv/MBq and 18.4 ± 5.1 µSv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5 ± 9.5 µSv/MBq (<i>L. crispatus</i>) and 66.7 ± 14.9 µSv/MBq (<i>E. coli</i>).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The whole-body ED for <i>L. crispatus</i> and <i>E. coli</i> is lower than reported values for ingested tracers, such as that from <sup>89</sup>Zr labelled antibodies and <sup>111</sup>In labelled “meals” used to determine gut transit times. Hence ingestion of <sup>89</sup>Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.</p>\n </section>\n </div>","PeriodicalId":18384,"journal":{"name":"Medical physics","volume":"52 9","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aapm.onlinelibrary.wiley.com/doi/epdf/10.1002/mp.18087","citationCount":"0","resultStr":"{\"title\":\"Biodistribution and dosimetry of 89Zirconium-labeled microbiota transplants in the pig gut\",\"authors\":\"Praveen Dassanayake, Diksha Diksha, Gabriel Varela-Mattatall, Qin Sun, Sarah C. Donnelly, Mojmir Suchy, Dianne Bartolome, Shaena Furlong, Lela Deans, Heather Biernaski, Yvonne Huston, R. Terry Thompson, Jeremy P. Burton, Gerald Moran, Neil Gelman, Frank S. Prato, Mike S. Kovacs, Jonathan D. Thiessen, Donna E. Goldhawk, James Schellenberg, Matthew S. Fox\",\"doi\":\"10.1002/mp.18087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as <i>Escherichia coli</i> Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Purpose</h3>\\n \\n <p>We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with <sup>89</sup>Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We administered <sup>89</sup>Zr-labeled <i>Lactobacillus crispatus</i> ATCC33820 (Gram-positive) to six female Duroc pigs (weight = 33.3 ± 4.6 kg) and <i>E. coli</i> Nissle 1917 (Gram-negative). Scans were performed between 6 h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7 ± 12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T<sub>2</sub>-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>PET imaging showed <sup>89</sup>Zr-labeled <i>L. crispatus</i> and <i>E. coli</i> post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for <sup>89</sup>Zr-labeled <i>L. crispatus</i> and <i>E. coli</i> were in the distal colon (26.8 ± 4.9 µSv/MBq and 28.4 ± 7.9 µSv/MBq, respectively) and proximal colon (17.9 ± 3.7 µSv/MBq and 18.4 ± 5.1 µSv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5 ± 9.5 µSv/MBq (<i>L. crispatus</i>) and 66.7 ± 14.9 µSv/MBq (<i>E. coli</i>).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The whole-body ED for <i>L. crispatus</i> and <i>E. coli</i> is lower than reported values for ingested tracers, such as that from <sup>89</sup>Zr labelled antibodies and <sup>111</sup>In labelled “meals” used to determine gut transit times. Hence ingestion of <sup>89</sup>Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18384,\"journal\":{\"name\":\"Medical physics\",\"volume\":\"52 9\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://aapm.onlinelibrary.wiley.com/doi/epdf/10.1002/mp.18087\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical physics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.18087\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical physics","FirstCategoryId":"3","ListUrlMain":"https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.18087","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Biodistribution and dosimetry of 89Zirconium-labeled microbiota transplants in the pig gut
Background
The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as Escherichia coli Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.
Purpose
We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with 89Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.
Methods
We administered 89Zr-labeled Lactobacillus crispatus ATCC33820 (Gram-positive) to six female Duroc pigs (weight = 33.3 ± 4.6 kg) and E. coli Nissle 1917 (Gram-negative). Scans were performed between 6 h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7 ± 12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T2-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.
Results
PET imaging showed 89Zr-labeled L. crispatus and E. coli post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for 89Zr-labeled L. crispatus and E. coli were in the distal colon (26.8 ± 4.9 µSv/MBq and 28.4 ± 7.9 µSv/MBq, respectively) and proximal colon (17.9 ± 3.7 µSv/MBq and 18.4 ± 5.1 µSv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5 ± 9.5 µSv/MBq (L. crispatus) and 66.7 ± 14.9 µSv/MBq (E. coli).
Conclusions
The whole-body ED for L. crispatus and E. coli is lower than reported values for ingested tracers, such as that from 89Zr labelled antibodies and 111In labelled “meals” used to determine gut transit times. Hence ingestion of 89Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.
期刊介绍：
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