Noninvasive detection of misfolded proteins in the brain using [11C]BF-227 PET

Nobuyuki Okamura, Katsutoshi Furukawa, Shozo Furumoto, Hiroyuki Arai, Manabu Tashiro, Yukitsuka Kudo, Kazuhiko Yanai

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Alzheimer's disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched β-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to β-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to α-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for β-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.

Original languageEnglish
Title of host publicationBioinformatics
Subtitle of host publicationConcepts, Methodologies, Tools, and Applications
PublisherIGI Global
Pages438-445
Number of pages8
Volume1
ISBN (Electronic)9781466636057
ISBN (Print)1466636041, 9781466636040
DOIs
Publication statusPublished - 2013 Mar 31

ASJC Scopus subject areas

  • Computer Science(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Noninvasive detection of misfolded proteins in the brain using [<sup>11</sup>C]BF-227 PET'. Together they form a unique fingerprint.

Cite this