Fig. 2: Compartmentalized antibiotic exposures in mouse studies.

Radioanalog of four antibiotics active against multidrug-resistant (MDR) Mycobacterium tuberculosis strains were utilized in mouse studies. Each radio analog is chemically identical to the respective parent antibiotic (panels a, d, g, j), and the radioisotope is retained within the major metabolite. Coronal, sagittal and transverse CT with PET AUC heatmap overlays (representing AUC_{tissue/plasma} ratio) from representative mice, demonstrating spatially compartmentalized antibiotic exposures in lung and brain compartments are shown for (b) ¹⁸F-pretomanid (AUC_0-60min), (e) ¹⁸F-sutezolid (AUC_0-60min), (h) ¹⁸F-linezolid (AUC_0-60min), and (k) ⁷⁶Br-bedaquiline (AUC_0-48h). Tissue-to-plasma ratios obtained using dynamic PET in live animals (AUC ratio) and by mass spectrometry (MS) from postmortem (tissue-to-plasma ratio) brain (red) and lung (blue) tissues are respectively shown for (c) ¹⁸F-pretomanid PET [AUC_0-60min ratio, data from four animals; n = 8 brain volumes of interest (VOIs), n = 8 lung VOIs], pretomanid MS (tissue/plasma ratio, data from six animals; n = 6 brain, n = 6 lung samples), (f) ¹⁸F-sutezolid PET (AUC_0-60min ratio, data from four animals; n = 8 brain VOIs, n = 8 lung VOIs), sutezolid MS (data from six animals; n = 6 brain, n = 6 lung samples), (i) ¹⁸F-linezolid PET (AUC_0-60min ratio, data from four animals; n = 8 brain VOIs, n = 8 lung VOIs), linezolid MS (data from six animals; n = 5 brain, n = 6 lung samples), and (l) ⁷⁶Br-Bedaquiline PET (AUC_0-48h ratio, data from three animals; n = 6 brain VOIs, n = 6 lung VOIs), bedaquiline MS (data from five animals; n = 5 brain, n = 5 lung samples). The horizontal dotted lines indicate a tissue/plasma ratio of 1. Data are represented as median ± interquartile range. Statistical comparisons were made using a two-tailed Mann-Whitney U test. Source data are provided as a Source Data file.