Figure 2

SUS enhances delivery of all RN2N antibody formats across the BBB. (A) Degree of Alexa-647 labeling of the antibody formats. (B) Quantification of Alexa Fluor 647-conjugated RN2N fluorescence intensity in peripheral organs of sonicated 2N tau-overexpressing pR5 mice using SUS (scanning ultrasound). The scFv produced a greater signal in the kidneys when compared to the IgG and Fab, whereas the other organs did not differ significantly (n = 5; mean ± SEM, two-way ANOVA with Tukey’s multiple comparisons test, ****P < 0.0001). (C) Alexa Fluor 647-conjugated RN2N was delivered to pR5 mice using SUS and including sham (microbubble injection, but no ultrasound treatment) as control. Brains were imaged with a Bruker In Vivo MS FX Pro optical imaging system with a 630 nm excitation filter and a 700 nm emission filter, and the fluorescence intensity was quantified and normalized to the degree of labeling. The fluorescence intensity of the IgG and Fab was greater than that of the scFv for both with or without SUS. The fluorescence intensity of all antibody formats was enhanced when delivery was combined with SUS (n = 5, mean ± SEM; student t-test, *P < 0.05, **P < 0.01).