Aromatic radiofluorination and biological evaluation of 2-aryl-6-[ 18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques

Byung Chul Lee, Ji Sun Kim, Bom Sahn Kim, Ji Yeon Son, Soo Kyung Hong, Hyun Soo Park, Byung Seok Moon, Jae Ho Jung, Jae Min Jeong, Sang Eun Kim

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (Ki = 5.5 nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Aβ plaques-specific positron emission tomography (PET) imaging probe, we investigated synthetic route suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t1/2 = 110 min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[18F]fluorobenzothiazoles ([18F]1-3) were synthesized in efficiently short reaction times (40-60 min) with high radiochemical yields (19-40%), purities (>95%) and specific activities (85-118 GBq/μmol). Tissue distribution studies showed that high radioactivity of [18F]2 accumulated in the brain with rapid clearance in healthy mice. Radioactive metabolites were analyzed in brain samples of mice and corresponded to 81% of parent remained by 30 min after a tail-vein injection. These results suggest that [18F]2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.

Original languageEnglish
Pages (from-to)2980-2990
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number9
DOIs
StatePublished - 1 May 2011

Keywords

  • Alzheimer's disease
  • Diaryliodonium salt
  • PET
  • β-Amyloid

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