Fig. 3: Post hoc exploratory analyses: 18F-FDG-PET/CT scans and transcriptional profiling. | Nature Medicine

Fig. 3: Post hoc exploratory analyses: 18F-FDG-PET/CT scans and transcriptional profiling.

From: A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial

Fig. 3

a, Representative 18F-FDG-PET/CT scan of a participant receiving GSK3036656 (ganfeborole) 30 mg at baseline (left column) and after 14 days of treatment (right column). Both scans are shown at a maximum scale of SUV 7. The axial slices shown at the top indicate the rapid response of a peri-cavitary lesion in the left inferior lobe, the sagittal slices shown in the middle indicate the response in cavities located in the superior and inferior lobes, and the coronal slices shown at the bottom indicate the response in and around the largest cavitary feature in this participant. b, Top: changes in TGA for each participant, computed from the sum of the body weight-adjusted SUV values per voxel, at day 14 versus baseline for those receiving GSK3036656 (ganfeborole) 30 mg (left) and GSK3036656 (ganfeborole) 1 mg (right). Bottom: changes in TAM, computed from the individual HU value per voxel + 1,000 to adjust for negative air values in the same participants. Data marked with an asterisk are from the participant illustrated in a. N by subject from left to right in the graph: N = 4,470, N = 4,824, N = 3,310, N = 4,916, N = 6,120, N = 755, N = 3,922, N = 1,459, N = 2,205, N = 2,826, N = 2,272, N = 1,626, N = 1,440, N = 2,531, N = 3,039, N = 7,701, N = 921, N = 944 and N = 3,971. Data are presented as mean values (± standard error of the mean). c, Heatmap of CIBERSORT gene expression profiles to estimate frequencies of each cell type. Mean values between participants in two groups: (1) those receiving GSK3036656 (ganfeborole) 1 mg; and (2) those receiving GSK3036656 (ganfeborole) 30 mg. d, Differential gene regulation at day 14 versus baseline for participants receiving GSK3036656 (ganfeborole) 1 mg (n = 7), GSK3036656 (ganfeborole) 30 mg (n = 13) and SOC (n = 13). Green indicates high log FC, but not significant, blue indicates significant but relatively low log FC, red indicates significant and high log FC, and gray indicates not significant, low log FC. 18F-FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography; CD, cluster of differentiation; FC, fold change; HU, Hounsfield units; NK, natural killer; NS, not significant; SOC, standard of care; SUV, standardized uptake value; TAM, total associated mass; TGA, total glycolytic activity.

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