Characterization of 18F-PM-PBB3 (18F-APN-1607) uptake in the rTg4510 mouse model of tauopathy

Chi Chang Weng, Ing Tsung Hsiao, Qing Fang Yang, Cheng Hsiang Yao, Chin Yin Tai, Meng Fang Wu, Tzu Chen Yen, Ming Kuei Jang, Kun Ju Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations

Abstract

Misfolding, aggregation, and cerebral accumulation of tau deposits are hallmark features of Alzheimer's disease. Positron emission tomography study of tau can facilitate the development of antitau treatment. Here, we investigated a novel tau tracer 18F-PM-PBB3 (18F-APN-1607) in a mouse model of tauopathy. Dynamic PET scans were collected in groups of rTg4510 transgenic mice at 2-11 months of age. Associations between distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) with cerebellum reference were used to determine the optimal scanning time and uptake pattern for each age. Immunohistochemistry staining of neurofibrillary tangles and autoradiography study was performed for ex vivo validation. An SUVR 40-70 min was most consistently correlated with DVR and was used in further analyses. Significant increased 18F-PM-PBB3 uptake in the brain cortex was found in six-month-old mice (+28.9%, p < 0.05), and increased further in the nine-month-old group (+38.8%, p < 0.01). The trend of increased SUVR value remained evident in the hippocampus and striatum regions except for cortex where uptake becomes slightly reduced in 11-month-old animals (+37.3%, p < 0.05). Radioactivity distributions from autoradiography correlate well to the presence of human tau (HT7 antibody) and hyperphosphorylated tau (antibody AT8) from the immunohistochemistry study of the adjacent brain sections. These findings supported that the 40-70 min 18F-PM-PBB3 PET scan with SUVR measurement can detect significantly increased tau deposits in a living rTg4510 transgenic mouse models as early as six-months-old. The result exhibited promising dynamic imaging capability of this novel tau tracer, and the above image characteristics should be considered in the design of longitudinal preclinical tau image studies.

Original languageEnglish
Article numbermolecules25071750
JournalMolecules
Volume25
Issue number7
DOIs
StatePublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors.

Keywords

  • Alzheimer's disease
  • F-APN-1607
  • F-FM-PBB3
  • Small animal PET
  • Tauopathy
  • Transgenic mice

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