Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences (SUND) is offering 3 three-year PhD fellowships in organic chemistry/radiopharmaceutical chemistry. The PhD fellowships are financed by the EU via a MC-ITN-ETN action. As such, the PhD fellowships are a part of a training programme PET-AlphaSy consisting in total 15 PhD students located in 5 European countries (Denmark, Sweden, Netherlands, Germany, Belgium). The PhD fellowships will attend common training sessions, e.g. within radiopharmaceutical chemistry or imaging and have secondments at the corresponding partner universities. The fellowships are available from 1 December 2018 or as soon as possible thereafter.
The positions are conditional on receiving the grant from the EU. Currently, the University of Copenhagen is within the negotiation phase with the EU.
- Project description
Nanomedicines have been proven to be beneficial in diagnosis and therapy. In vivo imaging studies with the help of labeled structures are crucial to develop new nanomedicinal based drugs. In this project, we will develop a new imaging method based on bioorthogonal chemistry. The tetrazine ligation will be used to establish a so called pretargeted imaging approach that will be applied to blood-brain-barrier (BBB) permeable antibodies. A set of tetrazines will be synthesized and evaluated in respect to reaction kinetics, ADME properties, BBB permeability and metabolism. Most promising compounds will be radiolabeled with fluorine-18 and subsequently evaluated in an in vivo system that will be developed within our MC-ITN-ETN network. The project is mainly organic chemistry focused and spiced up with radioactive work. BBB permeable antibodies will be provided from a small-medium sized enterprise, BioArctic, Sweden. In vivo evaluation studies will mainly be carried out at the Werner Siemens Imaging Center, Tuebingen, Germany. A 3 month stay abroad at both partners is requested.
Principal supervisor is Associate Professor, Matthias Herth, Department of Drug Design and Pharmacology, E-mail: email@example.com, Direct Phone: +45 93565414.
- Project description
Pretargeted imaging displays a novel possibility to image targets with monoclonal antibodies (mAb) with improved imaging contrast and lower radiation dose. The tetrazine ligation is one of the most promising bioorthogonal reaction for pretargeted strategies. In this project, a blood-brain-barrier (BBB) permeable antibody will be functionalized selectively with trans-cyclooctene (TCO) functional groups. These TCO groups will enable the selective binding of radiolabeled tetrazines to the mAb in vivo via pretargeted chemistry. Tetrazines will be developed by PhD fellows within our MC-ITN-ETN network and blood-brain-barrier (BBB) permeable antibodies will be provided by H. Lundbeck A/S, Denmark. In particular, this project is focused on novel strategic ideas to increase the amount of TCOs per mAb without disturbing the biological integrity of the mAb. Organic chemistry, ADME studies and biopharmaceutical chemistry techniques are the basis of this project. In vivo evaluation studies will mainly be carried out at the Uppsala University, Sweden and mAb conjugation chemistry at H. Lundbeck A/S, Denmark. Minimum 3 month stay at both partners is requested.