Prof. Simon Mensah Ametamey

 

Main Goals, Keywords

Radiopharmaceutical research and development is carried out by the Center for Radiopharmaceutical Science as a part of the PSI Life Science Department and the Professorship of Radiopharmacy at ETH together with the PET chemistry group at the USZ. The common theme consists of the search for radionuclide-labeled tracer molecules, which bind to specific targets in the body. Such radiopharmaceuticals are applied either systemically into the blood stream or locally to patients and due to their specific molecular binding properties combined with the emitted radiation, they allow to detect aberrant biochemical structures and functions. In addition they can be used to deliver cytotoxic radiation to tumour cells.

Keywords: PET-tracer, radioligand, in vivo imaging, in vivo pharmakokinetic, drug development

Group Members

1 Project Leader, 2 Ph.D. senior researchers, 2 Ph.D. postdocs, 2 engineers, 1 technician, P.D. students

Previous and Current Research

In an effort to improve our understanding of the processes involved in the progression of neurodegenerative diseases, our current research on PET/SPET- (PET=Positron Emission Tomography; SPET=Single Photon Emission Tomography) tracers allows the in vivo study of neurotransmitters, their metabolites and related enzymes. In order to examine the undisturbed physiological behaviour of molecules native to the body, the physiological and pharmacological parameters of the corresponding radiopharmaceutical must be identical or as close as possible to the natural substance. This is guaranteed when an available inactive atom within the natural substance can be substituted with a corresponding active isotope (e.g. 12C substituted by 11C). In this way precise quantitative tracer studies, which are the basis of an accurate diagnostic evaluation, can be made. However, in many cases this "isotope exchange" is not possible and one must resort to other radionuclides such as 18F or 123I. In such cases it is necessary to evaluate to which extent the altered radiopharmaceutical reflects the natural substance.
In the mammalian central nervous system (CNS) the glutamatergic NMDA-receptors plays a key role in mediating synaptic excitation. The NMDA-receptor is implicated in many neurological disease (eg. Stroke, Alzheimer's). Overactivation of this receptor triggers a cascade of events that leads to cell death. We are therefore interested in developing together with pharmaceutical companies radioligands that could be used to map the various binding sites of the NMDA-receptor complex using PET as imaging modality.
Furthermore radiotracers for the dopamine and serotonine transporter as well as for the nicotinergic receptor-system have been established with the goal of studying the effects of drug abuse (e.g. ecstasy).

Techniques and Equipment

Fully equipped laboratories (inactive and radioactive), PET-Cyclotron and PET-Scanner for animal and human studies.

Selected Publications

• Müller U, Ross TL, Ranadheera C, Slavik R, Müller A, Born M, Trauffer E, Sephton SM, Scapozza L, Krämer SD, Ametamey SM. Synthesis and preclinical evaluation of a new C-6 alkylated pyrimidine derivative as a PET imaging agent for HSV1-tk gene expression. Am J Nucl Med Mol Imaging. 2013;3(1):71-84. Epub 2013 Jan 5.
• Betzel T, Müller C, Groehn V, Müller A, Reber J, Fischer CR, Krämer SD, Schibli R, Ametamey SM. Radiosynthesis and preclinical evaluation of 3'-Aza-2'-[(18)F]fluorofolic acid: a novel PET radiotracer for folate receptor targeting. Bioconjug Chem. 2013 Feb 20;24(2):205-14. doi: 10.1021/bc300483a. Epub 2013 Jan 17.
• Milicevic Sephton S, Mu L, Schweizer WB, Schibli R, Kraemer S, Ametamey SM. Synthesis and Evaluation of Novel a-Fluorinated (E)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyl oxime (ABP688) Derivatives as Metabotropic Glutamate Receptor Subtype 5 PET Radiotracers. J Med Chem. 2012 Jul 23.