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

Yousefi BH, von Reutern B, Scherübl D, Manook A, Schwaiger M, Grimmer T, Henriksen G, Förster S, Drzezga A, Wester HJ - EJNMMI Res (2015)

Bottom Line: However, distinct study cohorts and different quantification techniques allow only for an indirect comparison between the different tracers.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).Moreover, the preclinical study design is recommendable for reliable assessment and comparison of novel radiopharmaceuticals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748 Garching, 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.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of the three Aβ radiopharmaceuticals used in this study.
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Sch1: Chemical structure of the three Aβ radiopharmaceuticals used in this study.

Mentions: In the current study, we employed this APP/PS1 mouse model for a direct comparison of two established and one newly developed Aβ PET tracer (Scheme 1). Among the 18F-labeled Aβ PET radiopharmaceuticals, [18F]florbetaben has shown good sensitivity and specificity for the detection of AD [42]. Hence, [18F]florbetaben was selected as reference 18F-radiopharmaceutical and compared with a promising in-house developed Aβ PET tracer [18F]FIBT [25,27] and the 11C-labeled gold standard [11C]PiB. In vivo small animal PET imaging and ex vivo validation experiments were carried out for ranking the tracers.Scheme 1


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

Yousefi BH, von Reutern B, Scherübl D, Manook A, Schwaiger M, Grimmer T, Henriksen G, Förster S, Drzezga A, Wester HJ - EJNMMI Res (2015)

Chemical structure of the three Aβ radiopharmaceuticals used in this study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402683&req=5

Sch1: Chemical structure of the three Aβ radiopharmaceuticals used in this study.
Mentions: In the current study, we employed this APP/PS1 mouse model for a direct comparison of two established and one newly developed Aβ PET tracer (Scheme 1). Among the 18F-labeled Aβ PET radiopharmaceuticals, [18F]florbetaben has shown good sensitivity and specificity for the detection of AD [42]. Hence, [18F]florbetaben was selected as reference 18F-radiopharmaceutical and compared with a promising in-house developed Aβ PET tracer [18F]FIBT [25,27] and the 11C-labeled gold standard [11C]PiB. In vivo small animal PET imaging and ex vivo validation experiments were carried out for ranking the tracers.Scheme 1

Bottom Line: However, distinct study cohorts and different quantification techniques allow only for an indirect comparison between the different tracers.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).Moreover, the preclinical study design is recommendable for reliable assessment and comparison of novel radiopharmaceuticals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748 Garching, 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.

No MeSH data available.


Related in: MedlinePlus