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Desorption Electrospray Ionization Mass Spectrometry Imaging of Cimbi-36, a 5-HT2A Receptor Agonist, with Direct Comparison to Autoradiography and Positron Emission Tomography

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Abstract

Purpose

The study demonstrates the use of Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) for imaging of the PET tracer compound Cimbi-36 in brain tissue and compares imaging by DESI-MSI to imaging by autoradiography and PET.

Procedures

Rats were dosed intraperitoneally with 3 mg/kg of Cimbi-36 and euthanized at t = 5, 10, 15, 30, 60 and 120 min post-injection. The brains were removed, frozen and sectioned, and sagittal sections were imaged by DESI-MSI in positive ion mode. Additionally, brain sections from a non-dosed animal were incubated with 14C-labelled Cimbi-36 and imaged by autoradiography. Finally, PET images were acquired from an animal dosed with 11C-labelled Cimbi-36.

Results

DESI-MSI and autoradiography images of a sagittal brain sections showed similar distributions of Cimbi-36, with increased abundance in the frontal cortex and choroid plexus, regions which are high in 5-HT2A and 5-HT2C receptors. The PET image also showed increased abundance in cortex, but the spatial resolution was clearly inferior to DESI-MSI and autoradiography.

The DESI-MSI results showed increased abundance of Cimbi-36 in brain tissue until 15 min, after which the abundance was declining. The PET-tracer was still clearly detectable at t = 120 min. Similar imaging of the kidneys showed the abundance of Cimbi-36 peaking at 30 min. Cimbi-36 was quantified in a t = 15 min brain section by quantitative DESI-MSI, resulting in tissue concentrations of 19.8 μg/g in cortex, 15.4 μg/g in cerebellum and 12.5 μg/g in whole brain.

Conclusions

DESI imaging from an in vivo dosing experiment showed distribution of the PET tracer remarkably similar to what was obtained by autoradiography of an in vitro incubation experiment, indicating that the obtained results represent actual binding to certain receptors in the brain. DESI-MSI is suggested as a cost-effective screening tool, which does not rely on labelling of compounds.

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Acknowledgements

Support from the Carlsberg Foundation and The Danish Council for Independent Research|Medical Sciences (grant no. DFF–4002-00391) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Sophie C. Jacobsen & Christian Janfelt

  2. Neurobiology Research Unit, Copenhagen University Hospital, Blegdamsvej 9, 2200, Copenhagen, Denmark

    Nikolaj R. Speth & Mikael Palner

  3. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Mengfei Xiong, Matthias M. Herth & Jesper L. Kristensen

  4. Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Blegdamsvej 9, 2200, Copenhagen, Denmark

    Mengfei Xiong & Matthias M. Herth

  5. Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark

    Mikael Palner

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  1. Sophie C. Jacobsen
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Contributions

JLK, MP and CJ developed the idea behind the project and designed the experiments. SCJ and NS performed the experiments and analysed the data under the supervision of JLK, MP and CJ. MX performed the PET scanning under supervision of MP and MMH. CJ wrote the original draft. CJ, MP, JLK and MMH reviewed and edited the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Christian Janfelt.

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Jacobsen, S.C., Speth, N.R., Xiong, M. et al. Desorption Electrospray Ionization Mass Spectrometry Imaging of Cimbi-36, a 5-HT2A Receptor Agonist, with Direct Comparison to Autoradiography and Positron Emission Tomography. Mol Imaging Biol 23, 676–685 (2021). https://doi.org/10.1007/s11307-021-01592-2

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  • DOI: https://doi.org/10.1007/s11307-021-01592-2

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