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Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice

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Abstract

Purpose

The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available.

Procedures

Five 13N-labelled azo compounds (1–5) were synthesized using a three-step process using cyclotron-produced [13N]NO3 −. Biodistribution studies were performed using positron emission tomography–computed tomography (PET–CT) on 20-month-old healthy, wild-type (WT) mice. In vivo and in vitro binding assays were performed using PET-CT and autoradiography, respectively, on 20-month-old healthy (WT) mice and transgenic (Tg2576) Alzheimer's disease model mice.

Results

13N-labelled azo compounds were prepared with decay corrected radiochemical yields in the range 27 ± 4 % to 39 ± 4 %. Biodistribution studies showed good blood–brain barrier penetration for compounds 1 and 3–5; good clearance data were also obtained for compounds 1–3 and 5. Compounds 2, 3 and 5 (but not 1) showed a significant uptake in β-amyloid-rich structures when assayed in in vitro autoradiographic studies. PET studies showed significant uptake of compounds 2 and 3 in the cortex of transgenic animals that exhibit β-amyloid deposits.

Conclusions

The results underscore the potential of compounds 2 and 3 as in vitro and in vivo markers for β-amyloid in animal models of Alzheimer's disease.

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Acknowledgments

This work was supported by EU grant PITN-GA-2012-316882 and by intramural FIMA (Fundación para la Investigación Médica Aplicada) funds. We acknowledge Dr. Juan Domingo Gispert for fruitful discussion about experimental design details.

Conflict of interest

None of the authors has any conflict of interest.

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Authors and Affiliations

  1. Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Vijay Gaja, Vanessa Gómez-Vallejo, Maria Puigivila, Carlos Pérez-Campaña & Jordi Llop

  2. Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Abraham Martin

  3. Division of Neuroscience, CIMA, University of Navarra, Pamplona, Spain

    Ana García-Osta, Mar Cuadrado-Tejedor & Rafael Franco

  4. Animal Facility, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Teresa Calvo-Fernández

  5. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain

    Rafael Franco

Authors
  1. Vijay Gaja
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  2. Vanessa Gómez-Vallejo
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  3. Maria Puigivila
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  4. Carlos Pérez-Campaña
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  5. Abraham Martin
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  7. Teresa Calvo-Fernández
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  8. Mar Cuadrado-Tejedor
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  9. Rafael Franco
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  10. Jordi Llop
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Corresponding author

Correspondence to Jordi Llop.

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Gaja, V., Gómez-Vallejo, V., Puigivila, M. et al. Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice. Mol Imaging Biol 16, 538–549 (2014). https://doi.org/10.1007/s11307-013-0708-x

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  • DOI: https://doi.org/10.1007/s11307-013-0708-x

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