Contact

Dr. Rares-Petru Moldovan

Wissen­­schaftlicher Mitarbei­ter Neuroradiopharmaka
Neuroradiopharmaceuticals
r.moldovanAthzdr.de
Phone: +49 351 260 4634

Dr. Winnie Deuther-Conrad

Research Associate
Neuroradiopharmaceuticals
w.deuther-conradAthzdr.de
Phone: +49 351 260 4613

New PET Radioligands for Imaging of Human Cannabinoid Receptors Type 2 (CB2) in the Brain -

Cannabinoid receptors are involved in many physiological mechanisms.

New PET Radioligands for Imaging of Human Cannabinoid Receptors Type 2 (CB2) in the Brain


Cannabinoid receptors are involved in many physiological mechanisms. There is evidence that cannabinoid receptors type 2 (CB2) play a central role in neurodegenerative disorders, like Alzheimer‘s or Parkinson‘s disease as well as in cancerous diseases. Thus, a therapeutic role for cannabinoid receptor ligands has been suggested for brain diseases and tumor treatment. By means of neuroimaging with positron emission tomography (PET), a better understanding of the involvement of the cannabinoid system in these diseases in living humans will be achieved. Furthermore, neuroimaging with 18F-labelled CB receptor ligands will be useful for monitoring treatment effects. Thus, radioligands selective for CB2, which are suitable for PET imaging in humans, are being developed. Employing molecular modeling methods, data were obtained by pharmacophore/3D-QSAR studies as additional constraints, which deliver valuable information on affinity and selectivity of the compounds towards CB1 and CB2.

Partner

  • Westfälische Wilhelms-Universität, Münster, Germany

  • Johns Hopkins University, Baltimore, USA

  • ETH Zurich, Zurich, Switzerland
  • KU Leuven, Belgium
  • Universität Leipzig

Latest Publications

  • Teodoro R., Gündel D., Deuther-Conrad W., Kazimir A., Toussaint M., Wenzel B., Bormans G., Hey-Hawkins E., Kopka K., Brust P, Moldovan R.-P. "Synthesis, Structure Activity Relationships, Radiofluorination and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET" J. Med. Chem. 2023, ASAP, https://doi.org/10.1021/acs.jmedchem.3c01035 

Foto: TOC ©Copyright: Dr. Rares-Petru Moldovan

  • Ueberham L., Gündel D., Kellert M., Deuther-Conrad W., Ludwig F.- A., Lönnecke P., Kazimir A., Kopka K., Brust P., Moldovan R.-P., Hey-Hawkins E., "Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [18F]LUZ5-d8" J. Med. Chem. 2023, 66, 7, 5242–5260. https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.3c00195 

  • Gündel, D.; Deuther-Conrad, W.; Ueberham, L.; Kaur, S.; Otikova, E.; Teodoro, R.; Lai, T. H.; Clauß, O.; Scheunemann, M.; Bormans, G.; Kopka, K.; Bachmann, M.; Brust, P., Moldovan R.-P. "Structure-based design, optimization, and development of [18F]LU13: A novel radioligand for cannabinoid receptor type 2 imaging in the brain with PET" J. Med. Chem. 2022, 65, 13, 9034–9049. https://doi.org/10.1021/acs.jmedchem.2c00256


  • Teodoro, R.; Gündel, D.; Ueberham, L.; Toussaint, M.; Bormans, G.; Brust, P.; Deuther-Conrad, W.; Moldovan, R.-P. "Development of [18F]LU14 for PET imaging of cannabinoid receptor type 2 in the brain" Int. J. Mol. Sci. 22(2021)15, 8051. https://doi.org/10.3390/ijms22158051 



  • Moldovan R.-P, Hausmann K., Deuther-Conrad W., Brust P. "Development of highly affine and selective fluorinated cannabinoid type 2 receptor ligands" ACS Med. Chem. Let. 2017,8, 566–571. https://doi.org/10.1021/acsmedchemlett.7b00129 


  • Moldovan R.-P., Deuther-Conrad W., Horti A., Brust P. "Synthesis and preliminary biological evaluation of indol-3-yl-oxoacetamides as potent cannabinoid receptor type 2 ligands" Molecules, 2017, 22, E77. https://doi.org/10.3390/molecules22010077 


  • Moldovan R.-P., Teodoro R., Gao Y.,  Deuther-Conrad W., Kranz M., Wang Y., Kuwabara H., Nakano M., Valentine H., Fischer S., Pomper M. G., Wong D. F., Dannals R. F., Brust P., Horti A. G. "Development of a High-Affinity PET Radioligand for Imaging Cannabinoid Subtype 2 Receptor" J. Med. Chem. 2016, 59, 17, 7840–7855 https://doi.org/10.1021/acs.jmedchem.6b00554 

Other Publications

  • Moldovan R.-P., Teodoro R., Deuther-Conrad W., Wang Y., Fischer S., Pomper M., Wong D. F., Dannals R. F., Brust P., Horti A. "[18F]JHU94620, a high affinity PET radioligand for imaging of cannabinoid subtype 2 receptors (CB2R)" J. Nucl. Med. 2015, 56, S3, 1048.
  • Donat C. K., Fischer F., Walter B., Deuther-Conrad W.,Bauer R., Brust P. "Early increase of cannabinoid receptor density after experimental traumatic brain injury in the newborn piglet" Acta Neurbiologiae Experimentalis. 2014, 74, 197-210.
  • Teodoro R, Moldovan R.-P., Lueg C, Günther R, Donat CK, Ludwig F-A, Fischer S, Deuther-Conrad W, Wünsch B, Brust P. "Synthesis, 18F-labelling and first biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB2 receptors."  Org Med Chem Lett. 2013, 3:11. https://doi.org/10.1186/2191-2858-3-11 
  • Rühl T., Deuther-Conrad W., Fischer S., Günther R., Hennig L., Krautscheid H., Brust P. "Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation" Org Med Chem Lett 2012, 2:32. https://doi.org/10.1186/2191-2858-2-32 

Financial Support by

  • Deutsche Forschungsgemeinschaft - DFG