Development of a PET tracer for the metabotropic glutamate receptor subtype 2

Project synopsis

The metabotropic glutamate receptors (mGluRs) comprise eight subtypes named mGlu1-8, which are believed to be involved in a wide range of neurological disorders and/or psychiatric diseases. At present selective mGlu2 negative allosteric modulators as well as mGlu2 antagonists have been explored as suitable PET ligands. However, in short, these do not meet with all requirements for a perfect PET ligand.

Our recent medicinal chemistry work has led us to discover the subtype-selective and super-potent mGlu2 orthosteric agonist LBG30300 (mGlu2-EC50= 0.6 nM), which also crosses the blood-brain-barrier (IV administration in mice). The work was just published in Journal of Medicinal Chemistry (https://doi.org/10.1021/acs.jmedchem.3c01811).

This translational research project will focus on the following objectives:

  1. Develop an expedite stereo-selective synthetic protocol for LBG30300 suitable for subsequent radiolabeling
  2. Synthesis of [3H]-LBG30300
  3. Develop radiochemical methodology for the synthesis of [11C]-LBG30300

Framework 

The mentor team spans expertise in design and synthesis of tool compounds for neuroscience studies, as well as 3H-labeling in general and thereof. The team also has a strong anchor in development/execution of radiochemistry and PET ligand synthesis (11C and 18F isotopes). At the clinical side, the mentor team works in compliance with GLP/GMP protocols required for PET ligand synthesis for human in vivo studies.

In summary, the mentor team represents a translational environment for the postdoc who wants to work at the cutting edge to develop novel diagnostic tools for neurological and/or psychiatric disorders.

Ideal candidate

    • PhD in organic chemistry or medicinal chemistry
    • Extensive hands-on experience with target-oriented synthesis
    • Desire to make significant contributions to treatment options for neurological and psychiatric disorders
    • Ideally, hands-on experience with radio-pharmaceutical chemistry
    • Ideally, insight into drug discovery for the brain

    Mentor team

    Basic mentor: Lennart Bunch, Professor in organic and medicinal chemistry, Department of Drug Design and Pharmacology, SUND/UCPH

    Clinical mentor: Tri H. V. Huynh, Head of Radiochemistry, Herlev Hospital (80%). Associate Professor at Dept. Drug Design and Pharmacology, SUND/UCPH (20%)

    Life science industry mentor: Philippe Huot, Associate Professor of Neurology and Neurosurgery, McGill University, Canada

    Contact 

    Lennart Bunch: lebu@sund.ku.dk