Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits

• Fuchigami, Takeshi

• Yamashita, Yuki

• Kawasaki, Masao

• Ogawa, Ayaka

• Haratake, Mamoru

• Atarashi, Ryuichiro

• Sano, Kazunori

• Nakagaki, Takehiro

• Ubagai, Kaori

• Ono, Masahiro

• Yoshida, Sakura

• Nishida, Noriyuki

• Nakayama, Morio

Abstract

Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrPSc). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrPSc. In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmol/nmol protein) than three other flavonoid derivatives (flavone, chalcone, and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrPSc-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC-OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiography experiments demonstrated high accumulation of [125I]SC-OMe and [125I]SC-(OMe)2 in prion deposit-rich regions of the mBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that [123I]SC-OMe showed consistent brain distribution with the presence of PrPSc deposits in the mBSE-infected mice brain. In conclusion, [123I]SC-OMe appears a promising SPECT radioligand for monitoring prion deposit levels in the living brain.

Journal

• Scientific Reports

  Scientific Reports 5 18440-, 2015-12-16

  Nature Publishing Group

Keywords

• Multidisciplinary

Details

• CRID: 1050001335835658624
• NII Article ID: 120005818252
• NII Article ID: 120006987233
• ISSN: 20452322
• DOI: 10.1038/srep18440
• HANDLE: 2433/215978
• HANDLE: 10069/36674
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/3509
• Web Site: https://www.nature.com/articles/srep18440
• Web Site: https://www.nature.com/articles/srep18440.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN