Biodistribution and dosimetry of 89Zirconium-labeled microbiota transplants in the pig gut

IF 3.2 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Medical physics Pub Date : 2025-09-03 DOI:10.1002/mp.18087

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

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引用次数: 0

Abstract

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.

Abstract Image

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89锆标记菌群在猪肠道内的生物分布及剂量学研究

胃肠道（GI）微生物群由多种微生物群落组成，对包括免疫调节在内的生理过程至关重要。像大肠杆菌Nissle 1917这样的菌株通过减少炎症和抵抗病原体来支持肠道健康。使用这类菌株的微生物治疗可能恢复胃肠道平衡，并提供抗生素的替代品，抗生素的过度使用会导致抗生素耐药性。然而，有效的治疗将需要优化递送和了解微生物的传播和植入。目的：我们开发了一种使用PET/MRI混合监测摄食后微生物迁移和胃肠道通透性的方法。为了模拟益生菌治疗，用89Zr对细菌进行放射性标记，包封后给猪注射。根据摄入后7天记录的时间活动曲线测定器官水平和全身剂量。方法用89zr标记的革兰氏阳性crispr乳杆菌ATCC33820（革兰氏阳性）和大肠杆菌Nissle 1917（革兰氏阴性）分别对体重为33.3±4.6 kg的杜洛克母猪进行免疫接种。使用混合PET/MRI系统在摄入后6小时至7天进行扫描。平均给药剂量为74.7±12.9 MBq。全身PET扫描与MRI同时进行，采用t2加权的HASTE序列。使用3d切片机处理图像，PET与MRI共同注册，并进行半自动器官分割。使用OLINDA计算性别平均人体等效器官水平有效剂量（ED）和全身ED。结果PET成像显示89zr标记的crispatus和大肠杆菌在摄入后主要定位于胃肠道，然后随粪便排出。89zr标记的crispatus和大肠杆菌平均ED最高的部位分别是结肠远端（分别为26.8±4.9µSv/MBq和28.4±7.9µSv/MBq）和结肠近端（分别为17.9±3.7µSv/MBq和18.4±5.1µSv/MBq）。其他器官ed较低。crispatus和大肠杆菌的全身ED分别为60.5±9.5µSv/MBq和66.7±14.9µSv/MBq。结论：crispatus和大肠杆菌的全身ED低于摄入示踪剂的报道值，例如用于测定肠道运输时间的89Zr标记抗体和111In标记“餐”。因此，摄入89Zr标记的细菌有望成为人类核医学程序，以确定益生菌治疗的有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical physics 医学-核医学

CiteScore

6.80

自引率

15.80%

发文量

660

审稿时长

1.7 months

期刊介绍： Medical Physics publishes original, high impact physics, imaging science, and engineering research that advances patient diagnosis and therapy through contributions in 1) Basic science developments with high potential for clinical translation 2) Clinical applications of cutting edge engineering and physics innovations 3) Broadly applicable and innovative clinical physics developments Medical Physics is a journal of global scope and reach. By publishing in Medical Physics your research will reach an international, multidisciplinary audience including practicing medical physicists as well as physics- and engineering based translational scientists. We work closely with authors of promising articles to improve their quality.