Fig. 5.

Different formats of bispecific, brain-penetrating antibodies used for PET imaging of Aβ pathology in AD transgenic mouse models. a F(ab’)₂ fragment of humanized Aβ protofibril-selective mAb158, chemically coupled to full 8D3 antibody (Mw ~270 kDa). b Recombinant variant of mAb158 (RmAb158) with scFv8D3 recombinantly fused to the C terminus of each of the light chains (Mw ~210 kDa). c Tribody composed of two scFv158 attached to each chain of a Fab-8D3, brought together by the natural combination of the Fab fragment (Mw ~110 kDa). d Tandem-scFv composed of scFv3D6 fused via a polypeptide linker to scFv8D3 (Mw ~58 kDa). e Blood elimination curves of recombinant antibody ligands (b), (c), and (d). The dashed red line represents an approximate antibody blood concentration threshold below which PET imaging is feasible. From the intersection of each antibody’s blood curve with the threshold line, there is a projection to a time window where AD transgenic mice can at the earliest be discriminated from wild-type mice