Abstract
BackgroundOver 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.MethodsA 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.ResultsWe 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).ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0090-6) contains supplementary material, which is available to authorized users.
Highlights
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
A new series of Aβ ligands, imidazo[2,1-b]benzothiazole (IBT), has been developed inspired by positive imaging results obtained in the IMPY and Pittsburgh compound B (PiB) studies
Human subjects Human data comes from preexisting studies at the Department of Nuclear Medicine with subjects who were recruited from the outpatient memory clinic of the Department of Psychiatry at the Technische Universität München (TUM)
Summary
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. Most of the published studies so far have relied on different methodologies and cohorts, and a direct comparison and ranking in a clinical setting is challenging for their different characteristics [29]. These limitations draw the attention to preclinical approaches for a direct intra-individual in vivo comparison of different 18F-labeled Aβ tracers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
