Challenges on Cyclic Nucleotide Phosphodiesterases Imaging with Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights since 2016

Int J Mol Sci. 2021 Apr 7;22(8):3832. doi: 10.3390/ijms22083832.

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) represent one of the key targets in the research field of intracellular signaling related to the second messenger molecules cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP). Hence, non-invasive imaging of this enzyme class by positron emission tomography (PET) using appropriate isoform-selective PDE radioligands is gaining importance. This methodology enables the in vivo diagnosis and staging of numerous diseases associated with altered PDE density or activity in the periphery and the central nervous system as well as the translational evaluation of novel PDE inhibitors as therapeutics. In this follow-up review, we summarize the efforts in the development of novel PDE radioligands and highlight (pre-)clinical insights from PET studies using already known PDE radioligands since 2016.

Keywords: PDE inhibitors; PDE radioligands; cyclic nucleotide phosphodiesterases; imaging; positron emission tomography; radiochemistry; recent (pre-)clinical insights.

Publication types

  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / chemistry*
  • 3',5'-Cyclic-GMP Phosphodiesterases / chemistry*
  • Animals
  • Humans
  • Ligands
  • Molecular Imaging*
  • Molecular Structure
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals

Substances

  • Ligands
  • Radiopharmaceuticals
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • 3',5'-Cyclic-GMP Phosphodiesterases