Assessment of brain beta-amyloid deposition in transgenic mouse models of Alzheimer's disease with PET imaging agents 18F-flutemetamol and 18F-florbetaben

BMC Neurosci. 2018 Jul 27;19(1):45. doi: 10.1186/s12868-018-0447-7.

Abstract

Background: Although amyloid beta (Aβ) imaging is widely used for diagnosing and monitoring Alzheimer's disease in clinical fields, paralleling comparison between 18F-flutemetamol and 18F-florbetaben was rarely attempted in AD mouse model. We performed a comparison of Aβ PET images between 18F-flutemetamol and 18F-florbetaben in a recently developed APPswe mouse model, C57BL/6-Tg (NSE-hAPPsw) Korl.

Results: After an injection (0.23 mCi) of 18F-flutemetamol and 18F-florbetaben at a time interval of 2-3 days, we compared group difference of SUVR and kinetic parameters between the AD (n = 7) and control (n = 7) mice, as well as between 18F-flutemetamol and 18F-florbetaben image. In addition, bio-distribution and histopathology were conducted. With visual image and VOI-based SUVR analysis, the AD group presented more prominent uptake than did the control group in both the 18F-florbetaben and 18F-flutemetamol images. With kinetic analysis, the 18F-florbetaben images showed differences in K1 and k4 between the AD and control groups, although 18F-flutemetamol images did not show significant difference. 18F-florbetaben images showed more prominent cortical uptake and matched well to the thioflavin S staining images than did the 18F-flutemetamol image. In contrast, 18F-flutemetamol images presented higher K1, k4, K1/k2 values than those of 18F-florbetaben images. Also, 18F-flutemetamol images presented prominent uptake in the bowel and bladder, consistent with higher bio-distribution in kidney, lung, blood and heart.

Conclusions: Compared with 18F-flutemetamol images, 18F-florbetaben images showed prominent visual uptake intensity, SUVR, and higher correlations with the pathology. In contrast, 18F-flutemetamol was more actively metabolized than was 18F-florbetaben (Son et al. in J Nucl Med 58(Suppl 1):S278, 2017].

Keywords: 18F-florbetaben; 18F-flutemetamol; Alzheimer’s disease; PET/CT imaging; transgenic mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds / pharmacology
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Brain Mapping*
  • Image Processing, Computer-Assisted* / methods
  • Male
  • Mice, Transgenic
  • Positron-Emission Tomography / methods
  • Stilbenes / pharmacology

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Stilbenes
  • 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene