Universität zu Köln

Yousefi, Behrooz H., von Reutern, Boris, Scheruebl, Daniela, Manook, Andre, Schwaiger, Markus, Grimmer, Timo, Henriksen, Gjermund, Foerster, Stefan, Drzezga, Alexander and Wester, Hans-Juergen (2015). FIBT versus florbetaben and PiB: a preclinical comparison study with amyloid-PET in transgenic mice. EJNMMI Res., 5. NEW YORK: SPRINGER. ISSN 2191-219X

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Abstract

Background: Over the last decade, an increasing number of studies have been published on the use of amyloid-beta (A beta) PET imaging with different F-18-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 A beta-targeted radiopharmaceuticals for PET imaging, including the newly developed agent [F-18]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 [F-18]FIBT, [F-18]florbetaben, and [C-11]PiB. The quantitative PET imaging data were cross-validated with the cerebral A beta plaque load as quantified ex vivo on histological sections. Results: We found that FIBT (2-(p-methylaminophenyl)-7-(2-[F-18] fluoroethoxy) imidazo[2,1-b]benzothiazole) compares favorably to florbetaben as a high-contrasting PET radiopharmaceutical for imaging A beta pathology. The excellent pharmacokinetics of FIBT in combination with its high-binding affinity towards A beta resulted in feasible high-contrast imaging of A beta 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 [F-18]FIBT, such as high initial brain uptake, fast clearance of the brain, and high binding affinity towards A beta as directly compared to the established amyloid tracers. Moreover, the preclinical study design is recommendable for reliable assessment and comparison of novel radiopharmaceuticals.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yousefi, Behrooz H. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Reutern, Boris UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheruebl, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Manook, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwaiger, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimmer, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Henriksen, Gjermund UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Wester, Hans-Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-404614
DOI:	10.1186/s13550-015-0090-6
Journal or Publication Title:	EJNMMI Res.
Volume:	5
Date:	2015
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	2191-219X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MOUSE MODEL; RADIATION-DOSIMETRY; BETA; DEPOSITION; C-11-PIB; BRAIN; F-18-FLORBETABEN Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40461