2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography

Johannes Schulte; Andreas Maurer; Lisa-Charlotte Domogalla; Nils Steinacker; Carolin Wadle; Johannes Kinzler; Matthias Eder; Constantin von Zur Mühlen; Marvin Krohn-Grimberghe; Ann-Christin Eder

doi:10.1093/infdis/jiae547

2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography

J Infect Dis. 2024 Nov 8:jiae547. doi: 10.1093/infdis/jiae547. Online ahead of print.

Authors

Johannes Schulte¹, Andreas Maurer^{2

3

4}, Lisa-Charlotte Domogalla^{5

6}, Nils Steinacker^{5

6}, Carolin Wadle¹, Johannes Kinzler², Matthias Eder^{5

6}, Constantin von Zur Mühlen¹, Marvin Krohn-Grimberghe^{1

7}, Ann-Christin Eder^{5

6}

Affiliations

¹ University Heart Center Freiburg - Bad Krozingen, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
³ Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tuebingen, Germany.
⁴ German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tuebingen, Tuebingen, Germany.
⁵ Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁶ Division of Radiopharmaceutical Development, German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany and German Cancer Research Center, Heidelberg, Germany.
⁷ Department of Cardiology, Ulm University Heart Center, University of Ulm, Ulm, Germany.

PMID: 39514763
DOI: 10.1093/infdis/jiae547

Abstract

Background: To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings. However, none of the methods used is capable of detecting the causative bacterial cells on the endothelium directly. Modern molecular imaging such as positron emission tomography/computed tomography (PET/CT) is playing an increasingly important role in unclear IE cases. This study focused on 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA), a bacteria specific tracer for the diagnosis of IE using PET imaging for direct pathogen detection.

Methods: In vitro assays were performed to analyze 2-[18F]F-PABA uptake by S. aureus. For proof-of-concept in vivo trials an endocarditis mouse model was used to diagnose IE by PET/Magnetic resonance (MR) imaging. A subcutaneous abscess mouse model was supplemented to create larger bacterial vegetations for PET imaging.

Results: 2-[18F]F-PABA in vitro uptake by S. aureus was confirmed. Only living bacteria were able to accumulate the tracer while the extent of uptake varied between different S. aureus strains. In the in vivo proof-of-concept, IE was visualized in mice using 2-[18F]F-PABA-PET/MR imaging. Subsequently, 2-[18F]F-PABA specifically located S. aureus vegetations in the subcutaneous abscess model.

Conclusions: This study highlights the great potential of 2-[18F]F-PABA imaging for the direct detection of IE. Future studies might further investigate the clinical potential of this molecular imaging approach, finally aiming at a clinical implementation.

Keywords: Staphylococcus aureus (S. aureus); 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA); Infective endocarditis; PET/MR imaging; folate; subcutaneous abscess.