Engineered antibodies for positron emission tomography imaging of neuroinflammation

Aim: As we live longer, more people will suffer from a neurodegenerative disease such as Alzheimer’s disease (AD).

Lack of methods to evaluate drug effects in clinical trials make it difficult to succeed in the search for new therapies.

This project aims to develop Positron Emission Tomography (PET) radioligands, utilizing bispecific antibodies (biAbs) engineered for efficient brain delivery.Status: We have previously showed that brain-penetrant biAbs can be radiolabelled and used with PET to detect amyloid-beta in brain.

We will now use this approach to develop PET radioligands based on biAbs for imaging of neuroinflammatory processes in the living brain.Work plan: First, we will assess targets expressed and upregulated by activated microglia and reactive astrocytes for PET imaging suitability.

Next, we will generate biAbs displaying affinity for both 1) proteins expressed by astrocytes or microglia and 2) receptors at the blood-brain barrier, facilitating active delivery into the brain.

Lastly, we will use these PET radioligands to visualize changes in neuroinflammation during AD progression and post-pharmacological intervention.

The project will be conducted in collaboration with the PET facilities at UU and the UU Hospital.Expected results: A novel class of PET radioligands for imaging of brain inflammation, i.e. an unmet need of today.

These radioligands will be important for understanding of mechanisms behind AD neuroinflammation, for diagnosis and for drug development.