PET Imaging in Preclinical Anti-Aβ Drug Development

Area of Science:

• Neuroscience
• Medical Imaging
• Pharmacology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation.
• Positron emission tomography (PET) is a crucial imaging modality for studying the brain in vivo.
• PET has demonstrated value in clinical trials for AD, including supporting the approval of aducanumab.

Purpose of the Study:

• To review the application of preclinical PET imaging in animal models of Aβ pathology for Alzheimer's disease drug development.
• To highlight the translatability of PET protocols between preclinical and clinical settings.
• To discuss the current and future role of PET in evaluating anti-Aβ therapies.

Main Methods:

• Focus on preclinical PET imaging studies utilizing genetically modified animal models expressing human Aβ.
• Emphasis on non-invasive, longitudinal imaging protocols.
• Review of PET's utility in assessing target engagement and treatment effects of anti-Aβ drug candidates.

Main Results:

• PET facilitates the detection of dose-dependent reductions in brain Aβ in response to therapeutic interventions.
• The translatability of PET allows for consistent study designs across species.
• Preclinical PET imaging supports the evaluation of novel anti-Aβ agents.

Conclusions:

• Preclinical PET imaging is a valuable tool in the development pipeline for Alzheimer's disease therapeutics.
• PET enables robust assessment of treatment efficacy in animal models, aiding translation to human studies.
• The continued application of PET in preclinical research is vital for advancing Aβ-targeting strategies for AD.