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EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Original research

FIBT versus florbetaben and PiB: a preclinical comparison study with amyloid-PET in transgenic mice

Authors: Behrooz H Yousefi, Boris von Reutern, Daniela Scherübl, André Manook, Markus Schwaiger, Timo Grimmer, Gjermund Henriksen, Stefan Förster, Alexander Drzezga, Hans-Jürgen Wester

Published in: EJNMMI Research | Issue 1/2015

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Abstract

Background

Over the last decade, an increasing number of studies have been published on the use of amyloid-β (Aβ) PET imaging with different 18F-radiopharmaceuticals for clinical characterization of Alzheimer’s disease (AD) in different stages. However, distinct study cohorts and different quantification techniques allow only for an indirect comparison between the different tracers. Thus, the aim of this study was the direct intra-individual in vivo comparison of different Aβ-targeted radiopharmaceuticals for PET imaging, including the newly developed agent [18F]FIBT.

Methods

A small group of four animals of a well-characterized APP/PS1 transgenic (tg) mouse model of AD and gender-matched control (ctl) animals underwent a sequential and standardized PET imaging regimen for direct comparison of [18F]FIBT, [18F]florbetaben, and [11C]PiB. The quantitative PET imaging data were cross-validated with the cerebral Aβ plaque load as quantified ex vivo on histological sections.

Results

We found that FIBT (2-(p-methylaminophenyl)-7-(2-[18F]fluoroethoxy)imidazo[2,1-b]benzothiazole) compares favorably to florbetaben as a high-contrasting PET radiopharmaceutical for imaging Aβ pathology. The excellent pharmacokinetics of FIBT in combination with its high-binding affinity towards Aβ resulted in feasible high-contrast imaging of Aβ with high global cortex to cerebellum standard uptake value ratio (SUVR) in 24-month-old tg mice (tg 1.68 ± 0.15 vs. ctl 0.95 ± 0.02). The SUVRs in transgenic versus control animals (SUVRtg/SUVRctl) for FIBT (1.78 ± 0.16) were similar to the ratios as observed in humans (SUVRAD/SUVRctl) for the established gold standard Pittsburgh compound B (PiB) (1.65 ± 0.41).

Conclusions

This head-to-head PET tracer comparison study in mice indicated the good imaging properties of [18F]FIBT, such as high initial brain uptake, fast clearance of the brain, and high binding affinity towards Aβ as directly compared to the established amyloid tracers. Moreover, the preclinical study design is recommendable for reliable assessment and comparison of novel radiopharmaceuticals.
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Metadata
Title
FIBT versus florbetaben and PiB: a preclinical comparison study with amyloid-PET in transgenic mice
Authors
Behrooz H Yousefi
Boris von Reutern
Daniela Scherübl
André Manook
Markus Schwaiger
Timo Grimmer
Gjermund Henriksen
Stefan Förster
Alexander Drzezga
Hans-Jürgen Wester
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0090-6

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