Applicability of [11C]PIB micro-PET imaging for in vivo follow-up of anti-amyloid treatment effects in APP23 mouse model

Neurobiol Aging. 2017 Sep:57:84-94. doi: 10.1016/j.neurobiolaging.2017.05.008. Epub 2017 May 15.

Abstract

In this study, we evaluated the anti-amyloid effect of functionalized nanoliposomes (mApoE-PA-LIP) in a mouse model of Alzheimer's disease with use of positron emission tomography and β-amyloid (Aβ)-targeted tracer [11C]Pittsburgh compound B ([11C]PIB). APP23 mice were injected with mApoE-PA-LIP or saline (3 times per week for 3 weeks) and [11C]PIB imaging was performed at baseline, after the treatment and after 3 months follow-up period, accompanied by Aβ immunohistochemistry and ELISA. After the treatment, [11C]PIB binding ratios between mApoE-PA-LIP and saline groups were equivalent in all analyzed brain regions; however, in the saline group, binding ratios increased from the baseline, whereas no increase was detected in the mApoE-PA-LIP group. During the additional follow-up, [11C]PIB binding increased significantly from baseline in both groups, and binding ratios correlated with the immunohistochemically defined Aβ load. This study further supports the use of [11C]PIB positron emission tomography imaging as a biomarker of Aβ deposition in APP23 mice and highlights the benefits of noninvasive follow-up, that is, using baseline data for animal stratification and normalization of treatment effects to baseline values, for future anti-amyloid treatment studies.

Keywords: APP23; Alzheimer's disease; Liposomes; PET; [(11)C]PIB; β-amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds*
  • Animals
  • Carbon Radioisotopes
  • Disease Models, Animal
  • Female
  • Follow-Up Studies
  • Humans
  • Liposomes / administration & dosage*
  • Liposomes / pharmacology
  • Liposomes / therapeutic use*
  • Male
  • Mice, Transgenic
  • Nanoparticles
  • Positron-Emission Tomography*
  • Radiopharmaceuticals
  • Thiazoles*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Carbon Radioisotopes
  • Liposomes
  • Radiopharmaceuticals
  • Thiazoles