Fig. 2: Enhanced brain uptake and biodistribution of ATVTfR and ATVCD98hc in the mouse brain and spinal cord by the whole-body fluorescence imaging.
a Representative images from AI-segmented 3D-reconstructed brains obtained from the whole-body tissue cleared mice dosed with AF647-conjugated control IgG, ATVTfR, or ATVCD98hc. arc. hypoth nuc arcuate hypothalamic nucleus, ventromed. hypoth nuc. ventromedial hypothalamic nucleus, median em. median eminence. Representative images from n = 3/group. b Mean fluorescence intensity (a.u.) of control IgG, ATVTfR, and ATVCD98hc as a function of brain depth from the cortical surface (0 μm) moving into deeper cortical tissues (1350 μm). n = 3/group, mean ± sem, two-tailed t-test with Benjamini–Hochberg false discovery rate control per depth bin, *p < 0.05, **p < 0.01, compared to control IgG, exact values provided in Source Data. Mean fluorescence intensity (a.u.) of AF647-conjugated control IgG (c), ATVTfR (d), or ATVCD98hc (e) across different mouse brain regions from the whole-body tissue cleared mice. n = 3/group, mean ± sem, two-tailed t-test with Benjamini–Hochberg false discovery rate control, all regions nonsignificant p value > 0.05 (mean fluorescence intensity of each brain region compared to whole brain average per treatment group). Top ten regions with highest fold change in fluorescence intensity compared to brain average fluorescence intensity for AF647-conjugated IgG (f), ATVTfR (g), or ATVCD98hc (h). Dotted line denotes the average brain intensity. n = 3/group, mean ± sem, two-tailed t-test with Benjamini–Hochberg false discovery rate control, subgeniculate nucleus adjusted p value 0.043, stria terminalis adjusted p value 0.024, arcuate hypothalamic nucleus adjusted p value 0.012 (mean fluorescence intensity of each brain region compared to whole brain average per treatment group). Optical slice longitudinal (i) or transverse (j) views of fluorescence images from mouse spinal cord from whole-body tissue cleared mice. Representative images from n = 3/group.
