Markus Staudt
Rapid Antibody-Based Positron Emission Tomography Imaging of Brain Targets
Markus Staudt, Department of Drug Design and Pharmacology at University of Copenhagen, has received a Lundbeck Foundation Postdoc grant worth DKK 2,497,948.
About the project
The blood brain barrier (BBB) only allows for a very specific subset of molecules to enter the brain. The development of radiolabeled agents for positron-emission tomography of brain targets is thus a time-consuming process. In contrast, highly specific monoclonal antibodies (mAb) or their single-chain variable fragments (scFv) can be developed within a relatively short amount of time.
Due to their size and polarity, mAb were until recently considered to be unsuitable for targeting proteins such as receptors within the brain. However, active transport e.g. via the transferrin receptor has recently been achieved, enabling transport of radiolabeled nanostructures into the brain. However, image contrast was low and selective binding could only be detected after three days. This is not surprising as only a limited amount of antibody can cross the BBB and excretion of circulating mAb in the blood remains slow. Consequently, long-lived radionuclides have to be used to align the biological half-life with the radioactive decay. This leads to unacceptably high radiation doses for patients or healthy subjects.
Therefore, this project aims at developing a cross-disciplinary new platform technology to accelerate the excretion of radionuclides from blood, thereby substantially increasing the target-to-background ratio. This will as such make mAb and scFv suitable for clinical imaging of neurologically important targets to improve the diagnosis and treatment of brain disorders.
