Radioligand Development

Contact person: Hanne D. Hansen

Positron Emission Tomography (PET) has unsurpassed sensitivity and specificity for measuring neurotransmitter receptors or other protein targets in the living human brain. At NRU we attempt to develop PET radioligands that enable novel and functional measures of different members of the serotonin receptor family. We have also recently engaged in measuring enzymatic proteins such as phosphodiesterases and histone deacetylases allowing us to investigate signal transduction and epigenetic mechanisms, respectively.

The process of PET radioligand development is a time and resource-demanding task that resembles that of pharmaceutical drug development in that promising compounds may fail at any stage of the sequential development process. The development process draws on highly specialized knowledge from fields such as medicinal chemistry, radiochemistry, and in vivo pharmacology. The phases that a PET radioligand for a given target undergoes involve: 1) chemical synthesis of cold ligands and in vitro test of which receptors the molecules bind to, 2) radiolabeling to incorporate a positron emitting isotope into the molecule, 3) in vitro and in vivo evaluation by testing the radiolabeled compound in the living brain of an experimental animal with PET.

The compounds that we develop into radioligands can be obtained through collaboration with the industry, other academic partners around the world, or synthesized from scratch by our close collaboration partner at the Department of Drug Design and Pharmaceuticals at University of Copenhagen.

Examples of recent publications:

  • Mandeville JB, Sander CY, Wey HY, Hooker JM, Hansen HD, Svarer C, Knudsen GM, Rosen BR. A regularized full reference tissue model for PET neuroreceptor mapping. Neuroimage. 2016 Jun 27;139:405-414
  • Herth MM, Petersen IN, Hansen HD, Hansen M, Ettrup A, Jensen AA, Lehel S, Dyssegaard A, Gillings N, Knudsen GM, Kristensen JL. Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands. Nucl Med Biol. 2016 Apr 19;43(8):455-462
  • Herth MM, Knudsen GM. Current radiosynthesis strategies for 5-HT2A receptor PET tracers. J Labelled Comp Radiopharm. 2015 Jun 15;58(7):265-73
  • Leth-Petersen S, Gabel-Jensen C, Gillings N, Lehel S, Hansen HD, Knudsen GM, Kristensen JL. Metabolic fate of hallucinogenic NBOMes. Chem Res Toxicol. 2016 Jan 19;29(1):96-100
  • Magnussen JH, Ettrup A, Donat CK, Peters D, Pedersen MHF, Knudsen GM, Mikkelsen JD. Radiosynthesis and in vitro validation of 3H-NS14492 as a novel high affinity alpha7 nicotinic receptor radioligand. Eur J Pharmacol. 2015 May 1; 762;35-41
  • Andersen VL, Hansen HD, Herth MM, Dyssegaard A, Knudsen GM, Kristensen JL. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand. Bioorg Med Chem Lett. 2015 Mar 1;25(5):1059-62
  • Hansen HD, Herth MM, Ettrup A, Andersen VL, Lehel S, Dyssegaard A, Kristensen JL, Knudsen GM. Radiosynthesis and In Vivo Evaluation of Novel Radioligands for PET Imaging of Cerebral 5-HT7 Receptors. J Nucl Med. 2014 Apr;55(4):640-6
  • Risgaard R, Ettrup A, Balle T, Dyssegaard A, Hansen HD, Lehel S, Madsen J, Pedersen H, Püschl A, Badolo L, Bang-Andersen B, Knudsen GM, Kristensen JL. Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936. Nuclear Medicine and Biology. 2013 Jan;40(1):135-40
  • Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM. Radiosynthesis and in vivo evaluation of a series of substituted (11)C-phenethylamines as 5-HT (2A) agonist PET tracers. Eur J Nucl Med Mol Imaging. 2011;38(4):681-93