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

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

doi:10.1186/s13550-015-0090-6

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

EJNMMI Res. 2015 Mar 28:5:20. doi: 10.1186/s13550-015-0090-6. eCollection 2015.

Affiliations

¹ Department of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748 Garching, Germany.
² Department of Nuclear Medicine, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany ; Institute of Neuroscience and Medicine (INM-3), Research Centre Jülich, Wilhelm-Johnen-Straße, 52428 Jülich, Germany.
³ Department of Nuclear Medicine, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany.
⁴ Department of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748 Garching, Germany ; Department of Nuclear Medicine, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany.
⁵ Department of Psychiatry and Psychotherapy, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany.
⁶ Department of Nuclear Medicine, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany ; Department of Nuclear Medicine, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.

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 (18)F-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 [(18)F]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 [(18)F]FIBT, [(18)F]florbetaben, and [(11)C]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-[(18)F]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 [(18)F]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.

Keywords: APP/PS1 transgenic mouse animal model of AD; Alzheimer’s disease; Autoradiography; FIBT; Florbetaben; In vivo imaging; In vivo radiotracers ranking; PiB; Small-animal PET; β-amyloid.