The Alzheimer's disease 5xFAD mouse model is best suited to investigate pretargeted imaging approaches beyond the blood-brain barrier

Alzheimer's disease (AD) is the most common neurodegenerative disease, with an increasing prevalence. Currently, there no ideal diagnostic molecular imaging agent for diagnosing AD. Antibodies (Abs) have been proposed to close this gap as they can bind selectively and high affinity amyloid β (Aβ)—one of hallmarks Abs even be designed Aβ oligomers or isoforms, which are difficult target small agents. Conventionally, must labeled long-lived radionuclides typically results in radiation burden healthy tissue. Pretargeted could solve challenge it allows use short-lived radionuclides. To develop pretargeted tools that enter brain, AD mouse models useful allow testing approach a relevant animal model predict its clinical applicability. Several developed different characteristics. Commonly used are: 5xFAD, APP/PS1 tg-ArcSwe transgenic mice. In study, we aimed identify these were best suited investigate approaches beyond blood brain barrier. We evaluated by autoradiography using Aβ-targeting antibody 3D6 111 In-labeled Tz. Evaluation criteria target-to-background ratios accessibility. mice showed accumulation low binding regions such less suitable purposes. 5xFAD similar uptake whereas better evaluate approaches. advantaged over pathology traced early (6 months compared 18 age) commercially available.