Yuderleys Masias-Leon, Carlos E Ruiz-Gonzalez, Oscar J Nino-Meza, Medha Singh, Mona O Sarhan, Xueyi Chen, Kelly Flavahan, Amy Kronenberg, Elizabeth W Tucker, Joel S Freundlich, Martin A Lodge, Laurence S Carroll, Nicole Parrish, Noah Lechtzin, Sanjay K Jain
{"title":"用于观察肺分枝杆菌脓肿感染的动态 11C-PABA PET/CT","authors":"Yuderleys Masias-Leon, Carlos E Ruiz-Gonzalez, Oscar J Nino-Meza, Medha Singh, Mona O Sarhan, Xueyi Chen, Kelly Flavahan, Amy Kronenberg, Elizabeth W Tucker, Joel S Freundlich, Martin A Lodge, Laurence S Carroll, Nicole Parrish, Noah Lechtzin, Sanjay K Jain","doi":"10.1164/rccm.202409-1792OC","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong><i>Mycobacteroides abscessus</i> infections affect immunocompromised patients and those with underlying pulmonary disease. Conventional imaging cannot distinguish <i>M. abscessus</i> infections from underlying pulmonary disease or sterile inflammation, requiring invasive procedures for definitive diagnosis.</p><p><strong>Objective: </strong>We evaluated <sup>11</sup>C-<i>para</i>-aminobenzoic acid (<sup>11</sup>C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to <i>M. abscessus</i>.</p><p><strong>Methods: </strong><i>In vitro</i> uptake assays were performed to test the metabolism and accumulation of PABA into <i>M. abscessus</i> reference and clinical isolates. Dynamic <sup>11</sup>C-PABA positron emission tomography (PET) was performed in a mouse model of <i>M. abscessus</i> pulmonary infection and in a patient with microbiologically-confirmed <i>M. abscessus</i> pulmonary infection (NCT05611905).</p><p><strong>Main results: </strong><sup>11</sup>C-PABA was intracellularly metabolized by <i>M. abscessus</i> to <sup>11</sup>C-7,8-dihydropteroate. Additionally, and the reference and all thirteen randomly chosen clinical isolates, including three resistant to trimethoprim-sulfamethoxazole, rapidly accumulated PABA. No PABA accumulation was noted by heat-inactivated bacteria or mammalian cells. Dynamic <sup>11</sup>C-PABA PET in a mouse model of <i>M. abscessus</i> pulmonary infection rapidly distinguished infection from sterile inflammation and also accurately monitored response to antibiotic treatment. Finally, dynamic <sup>11</sup>C-PABA PET in a 33-year-old female with cystic fibrosis and microbiologically confirmed <i>M. abscessus</i> pulmonary infection was safe and demonstrated significantly higher and sustained PET uptake in the affected lesions.</p><p><strong>Conclusions: </strong><sup>11</sup>C-PABA PET is an innovative, clinically-translatable, noninvasive, bacteria-specific diagnostic to differentiate <i>M. abscessus</i> infections from underlying pulmonary disease in patients. This tool could also help in monitoring treatment responses and enable precision medicine approaches for patients with complicated infections. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.3000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dynamic <sup>11</sup>C-PABA PET/CT for Visualizing Pulmonary <i>Mycobacteroides abscessus</i> Infections.\",\"authors\":\"Yuderleys Masias-Leon, Carlos E Ruiz-Gonzalez, Oscar J Nino-Meza, Medha Singh, Mona O Sarhan, Xueyi Chen, Kelly Flavahan, Amy Kronenberg, Elizabeth W Tucker, Joel S Freundlich, Martin A Lodge, Laurence S Carroll, Nicole Parrish, Noah Lechtzin, Sanjay K Jain\",\"doi\":\"10.1164/rccm.202409-1792OC\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong><i>Mycobacteroides abscessus</i> infections affect immunocompromised patients and those with underlying pulmonary disease. Conventional imaging cannot distinguish <i>M. abscessus</i> infections from underlying pulmonary disease or sterile inflammation, requiring invasive procedures for definitive diagnosis.</p><p><strong>Objective: </strong>We evaluated <sup>11</sup>C-<i>para</i>-aminobenzoic acid (<sup>11</sup>C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to <i>M. abscessus</i>.</p><p><strong>Methods: </strong><i>In vitro</i> uptake assays were performed to test the metabolism and accumulation of PABA into <i>M. abscessus</i> reference and clinical isolates. Dynamic <sup>11</sup>C-PABA positron emission tomography (PET) was performed in a mouse model of <i>M. abscessus</i> pulmonary infection and in a patient with microbiologically-confirmed <i>M. abscessus</i> pulmonary infection (NCT05611905).</p><p><strong>Main results: </strong><sup>11</sup>C-PABA was intracellularly metabolized by <i>M. abscessus</i> to <sup>11</sup>C-7,8-dihydropteroate. Additionally, and the reference and all thirteen randomly chosen clinical isolates, including three resistant to trimethoprim-sulfamethoxazole, rapidly accumulated PABA. No PABA accumulation was noted by heat-inactivated bacteria or mammalian cells. Dynamic <sup>11</sup>C-PABA PET in a mouse model of <i>M. abscessus</i> pulmonary infection rapidly distinguished infection from sterile inflammation and also accurately monitored response to antibiotic treatment. Finally, dynamic <sup>11</sup>C-PABA PET in a 33-year-old female with cystic fibrosis and microbiologically confirmed <i>M. abscessus</i> pulmonary infection was safe and demonstrated significantly higher and sustained PET uptake in the affected lesions.</p><p><strong>Conclusions: </strong><sup>11</sup>C-PABA PET is an innovative, clinically-translatable, noninvasive, bacteria-specific diagnostic to differentiate <i>M. abscessus</i> infections from underlying pulmonary disease in patients. This tool could also help in monitoring treatment responses and enable precision medicine approaches for patients with complicated infections. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>\",\"PeriodicalId\":7664,\"journal\":{\"name\":\"American journal of respiratory and critical care medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":19.3000,\"publicationDate\":\"2025-03-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of respiratory and critical care medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1164/rccm.202409-1792OC\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of respiratory and critical care medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1164/rccm.202409-1792OC","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Dynamic 11C-PABA PET/CT for Visualizing Pulmonary Mycobacteroides abscessus Infections.
Rationale: Mycobacteroides abscessus infections affect immunocompromised patients and those with underlying pulmonary disease. Conventional imaging cannot distinguish M. abscessus infections from underlying pulmonary disease or sterile inflammation, requiring invasive procedures for definitive diagnosis.
Objective: We evaluated 11C-para-aminobenzoic acid (11C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to M. abscessus.
Methods: In vitro uptake assays were performed to test the metabolism and accumulation of PABA into M. abscessus reference and clinical isolates. Dynamic 11C-PABA positron emission tomography (PET) was performed in a mouse model of M. abscessus pulmonary infection and in a patient with microbiologically-confirmed M. abscessus pulmonary infection (NCT05611905).
Main results: 11C-PABA was intracellularly metabolized by M. abscessus to 11C-7,8-dihydropteroate. Additionally, and the reference and all thirteen randomly chosen clinical isolates, including three resistant to trimethoprim-sulfamethoxazole, rapidly accumulated PABA. No PABA accumulation was noted by heat-inactivated bacteria or mammalian cells. Dynamic 11C-PABA PET in a mouse model of M. abscessus pulmonary infection rapidly distinguished infection from sterile inflammation and also accurately monitored response to antibiotic treatment. Finally, dynamic 11C-PABA PET in a 33-year-old female with cystic fibrosis and microbiologically confirmed M. abscessus pulmonary infection was safe and demonstrated significantly higher and sustained PET uptake in the affected lesions.
Conclusions: 11C-PABA PET is an innovative, clinically-translatable, noninvasive, bacteria-specific diagnostic to differentiate M. abscessus infections from underlying pulmonary disease in patients. This tool could also help in monitoring treatment responses and enable precision medicine approaches for patients with complicated infections. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
期刊介绍：
The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences.
A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.
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