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/).
American Journal of Respiratory and Critical Care Medicine
Dynamic 11C-PABA PET/CT for Visualizing Pulmonary Mycobacteroides abscessus Infections
Yuderleys Masias-Leon
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, Carlos E. Ruiz-Gonzalez Yuderleys Masias-Leon
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Oscar J. Nino-Meza Carlos E. Ruiz-Gonzalez
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Medha Singh Oscar J. Nino-Meza
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Mona O. Sarhan Medha Singh
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Xueyi Chen Mona O. Sarhan
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Kelly Flavahan Xueyi Chen
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Amy Kronenberg Kelly Flavahan
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
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, Elizabeth W. Tucker Amy Kronenberg
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Johns Hopkins School of Medicine, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Baltimore, Maryland, United States
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, Joel S. Freundlich Elizabeth W. Tucker
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Johns Hopkins School of Medicine, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Baltimore, Maryland, United States
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, Martin A. Lodge Joel S. Freundlich
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, Martin A. Lodge
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Johns Hopkins University, Nuclear Medicine, Baltimore, Maryland, United States
Johns Hopkins University, Nuclear Medicine, Baltimore, Maryland, United States
Laurence S. Carroll
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, Nicole Parrish Laurence S. Carroll
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Johns Hopkins School of Medicine, Radiology, Baltimore, Maryland, United States
Johns Hopkins School of Medicine, Radiology, Baltimore, Maryland, United States
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, Noah Lechtzin Nicole Parrish
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Johns Hopkins Medicine School of Medicine, Pathology, Baltimore, Maryland, United States
Johns Hopkins Medicine School of Medicine, Pathology, Baltimore, Maryland, United States
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, and Sanjay K Jain Noah Lechtzin
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Johns Hopkins Hospital, Pulmonary Critical Care, Baltimore, Maryland, United States
Johns Hopkins Hospital, Pulmonary Critical Care, Baltimore, Maryland, United States
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Sanjay K Jain
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Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States; [email protected]
Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States; [email protected]
- Yuderleys Masias-Leon Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Carlos E. Ruiz-Gonzalez Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Oscar J. Nino-Meza Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Medha Singh Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Mona O. Sarhan Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Xueyi Chen Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Kelly Flavahan Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
- Amy Kronenberg Johns Hopkins School of Medicine, Baltimore, Maryland, United States
- Elizabeth W. Tucker Johns Hopkins School of Medicine, Baltimore, Maryland, United States
- Joel S. Freundlich Rutgers University, New Brunswick, New Jersey, United States
- Martin A. Lodge Johns Hopkins University, Nuclear Medicine, Baltimore, Maryland, United States
- Laurence S. Carroll Johns Hopkins School of Medicine, Radiology, Baltimore, Maryland, United States
- Nicole Parrish Johns Hopkins Medicine School of Medicine, Pathology, Baltimore, Maryland, United States
- Noah Lechtzin Johns Hopkins Hospital, Pulmonary Critical Care, Baltimore, Maryland, United States
- Sanjay K Jain Johns Hopkins School of Medicine, Pediatrics, Baltimore, Maryland, United States
Received: September 19, 2024
Accepted: March 26, 2025