Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET

J Med Chem. 2009 Feb 12;52(3):688-99. doi: 10.1021/jm8011855.

Abstract

Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared, and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new 18F-labeled PBR radioligand, namely [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]9). [18F]9 was produced easily through a single and highly efficient step, the reaction of [18F]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [18F]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [18F]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [18F]2-fluoro-N-(2-phenoxyphenyl)acetamide ([18F]11). [18F]9 is a promising radioligand for future imaging of PBR in living human brain.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acetanilides / chemical synthesis
  • Acetanilides / chemistry*
  • Acetanilides / pharmacology*
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Fluorine Radioisotopes
  • Humans
  • Macaca mulatta
  • Male
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / chemical synthesis
  • Rats
  • Receptors, GABA-A / metabolism*

Substances

  • Acetanilides
  • Fluorine Radioisotopes
  • N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
  • Radiopharmaceuticals
  • Receptors, GABA-A