A Facile Radiolabeling of [18F]FDPA via Spirocyclic Iodonium Ylides: Preliminary PET Imaging Studies in Preclinical Models of Neuroinflammation

J Med Chem. 2017 Jun 22;60(12):5222-5227. doi: 10.1021/acs.jmedchem.7b00432. Epub 2017 Jun 5.

Abstract

A suitable TSPO PET ligand may visualize and quantify neuroinflammation in a living brain. Herein we report a 18F-ligand, [18F]2 ([18F]FDPA), is radiolabeled in high yield and high specific activity based on our spirocyclic iodonium ylide (SCIDY) strategy. [18F]2 demonstrated saturable specific binding to TSPO, substantially elevated brain uptake, and slow washout of bound PET signal in the preclinical models of brain neuroinflammation (cerebral ischemia and Alzheimer's disease).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoradiography
  • Brain / diagnostic imaging
  • Brain / pathology
  • Carrier Proteins / metabolism*
  • Chemistry Techniques, Synthetic
  • Contrast Media
  • Disease Models, Animal
  • Encephalitis / diagnostic imaging*
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics
  • Isotope Labeling / methods*
  • Mice, Transgenic
  • Onium Compounds / chemistry
  • Positron-Emission Tomography / methods*
  • Pyrazoles / chemistry
  • Pyrimidines / chemistry
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Tissue Distribution

Substances

  • Carrier Proteins
  • Contrast Media
  • Fluorine Radioisotopes
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Onium Compounds
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA-A
  • Tspo protein, rat