ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein.

ABSTRACT:

Background

Hijacking the transferrin receptor (TfR) is an effective strategy to transport amyloid-beta (Aβ) immuno-positron emission tomography (immunoPET) ligands across the blood-brain barrier (BBB). Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβ pathology in mouse models of Alzheimer's disease (AD). This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands.

Methods

Two affinity variants of the rat TfR antibody, OX26, were chemically conjugated to a F(ab')₂ fragment of the anti-Aβ antibody, bapineuzumab (Bapi), to generate two bispecific fusion proteins: OX26₅-F(ab')₂-Bapi and OX26₇₆

SUBMITTER: Bonvicini G 

PROVIDER: S-EPMC9791759 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature