Synthesis, radiolabeling, and in vivo pharmacokinetic evaluation of the amyloid beta radioligand [11C]AZD4694 in nonhuman primates.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 101125610 Publication Model: Print Cited Medium: Internet ISSN: 1860-2002 (Electronic) Linking ISSN: 15361632 NLM ISO Abbreviation: Mol Imaging Biol Subsets: MEDLINE
    • Publication Information:
      Publication: 2005- : New York, NY : Springer
      Original Publication: New York, NY : Elsevier Science, c2001-
    • Subject Terms:
      Amyloid beta-Peptides/*chemical synthesis ; Amyloid beta-Peptides/*pharmacokinetics ; Benzofurans/*chemical synthesis ; Benzofurans/*pharmacokinetics ; Hydrocarbons, Fluorinated/*chemical synthesis ; Hydrocarbons, Fluorinated/*pharmacokinetics ; Macaca fascicularis/*metabolism ; Radiopharmaceuticals/*chemical synthesis ; Radiopharmaceuticals/*pharmacokinetics; Aniline Compounds/blood ; Aniline Compounds/pharmacokinetics ; Animals ; Benzofurans/blood ; Brain/diagnostic imaging ; Carbon Radioisotopes ; Humans ; Hydrocarbons, Fluorinated/blood ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Radiopharmaceuticals/blood ; Thiazoles/blood ; Thiazoles/pharmacokinetics ; Time Factors
    • Abstract:
      Purpose: [(18)F]AZD4694 (2-(2-(18)F-fluoro-6-(methylamino)-3-pyridyl)benzofuran-5-ol) is a radioligand suitable for imaging of amyloid beta deposits in the living human brain using positron emission tomography (PET). Here, we report the preparation and pharmacokinetic profile of its carbon-11 (t1/2 = 20.4 min) labeled isotopolog [(11)C]AZD4694 and compare [(11)C]AZD4694 with the hitherto most widely applied amyloid PET radioligand [(11)C]Pittsburgh Compound B (PiB).
      Procedures: The immediate unlabeled precursor to [(11)C]AZD4694 was prepared in a four-step convergent synthesis. Subsequent N-(11)C-methylation of this precursor with [(11)C]methyl iodide yielded [(11)C]AZD4694, which after isolation and formulation was injected into cynomolgus monkeys. The radioactivity in nonhuman primate brain following injection of [(11)C]AZD4694 and [(11)C]PiB was measured using PET.
      Results: [(11)C]AZD4694 was prepared in a 60 % incorporation yield. In a head to head comparison with [(11)C]PiB, it appeared that [(11)C]AZD4694 displayed slightly lower nonspecific binding in white matter than [(11)C]PiB as well as more rapid pharmacokinetics in the brain.
      Conclusions: The advantageous pharmacokinetic profile and low nonspecific binding render [(11)C]AZD4694 a promising PET radioligand for imaging of amyloid beta in the human brain with PET.
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    • Accession Number:
      0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole)
      0 (AZD4694)
      0 (Amyloid beta-Peptides)
      0 (Aniline Compounds)
      0 (Benzofurans)
      0 (Carbon Radioisotopes)
      0 (Hydrocarbons, Fluorinated)
      0 (Radiopharmaceuticals)
      0 (Thiazoles)
    • Publication Date:
      Date Created: 20130905 Date Completed: 20141112 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      10.1007/s11307-013-0666-3
    • Accession Number:
      24002613