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Suitability of [18F]Altanserin and PET to Determine 5-HT2A Receptor Availability in the Rat Brain: In Vivo and In Vitro Validation of Invasive and Non-Invasive Kinetic Models

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Abstract

Purpose

While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.

Procedures

Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals.

Result

Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals.

Conclusion

[18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.

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Acknowledgments

Magdalene Vögeling, Sabine Wilms, Babara Elghahwagi, and Dorothe Krug are gratefully acknowledged for their excellent technical assistance. Claudia Kuntner kindly provided the software for time-logging of blood sampling. We thank Nikola Kornadt-Beck for valuable discussions. Tanja Juraschek, Steffi Holz, and Larissa Damm took care of the animal housing. Johannes Ermert and Heinz H. Coenen are gratefully acknowledged for the supply of the radioligand as well as Avdo Celik and N. Jon Shah for providing MRI equipment.

Disclosure/Conflict of Interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich GmbH, Jülich, 52425, Germany

    Tina Kroll, David Elmenhorst, Andreas Matusch, Franziska Wedekind, Angela Weisshaupt, Simone Beer & Andreas Bauer

  2. Central Institute for Electronics, Forschungszentrum Jülich GmbH, Jülich, 52425, Germany

    Simone Beer

  3. Neurological Department, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Andreas Bauer

Authors
  1. Tina Kroll
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  2. David Elmenhorst
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  5. Angela Weisshaupt
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  6. Simone Beer
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  7. Andreas Bauer
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Correspondence to Tina Kroll.

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Kroll, T., Elmenhorst, D., Matusch, A. et al. Suitability of [18F]Altanserin and PET to Determine 5-HT2A Receptor Availability in the Rat Brain: In Vivo and In Vitro Validation of Invasive and Non-Invasive Kinetic Models. Mol Imaging Biol 15, 456–467 (2013). https://doi.org/10.1007/s11307-013-0621-3

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  • DOI: https://doi.org/10.1007/s11307-013-0621-3

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