Dynamic ¹¹C-<i>Para</i>-Aminobenzoic Acid Positron Emission Tomography/Computed Tomography for Visualizing Pulmonary <i>Mycobacteroides abscessus</i> Infections.

Abstract

<b>Rationale:</b> <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. <b>Objectives:</b> We evaluated ¹¹C-<i>para</i>-aminobenzoic acid (¹¹C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to <i>M. abscessus</i>. <b>Methods:</b> <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 ¹¹C-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). <b>Measurements and Main Results:</b> ¹¹C-PABA was intracellularly metabolized by <i>M. abscessus</i> to ¹¹C-7,8-dihydropteroate. In addition, the reference strain and all 13 randomly chosen clinical isolates, including 3 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 <i>M. abscessus</i> 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 woman 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. <b>Conclusions:</b> ¹¹C-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.