Loading…

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

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...

Full description

Saved in:
Bibliographic Details
Published in:Molecular imaging and biology 2021-10, Vol.23 (5), p.676-685
Main Authors: Jacobsen, Sophie C., Speth, Nikolaj R., Xiong, Mengfei, Herth, Matthias M., Kristensen, Jesper L., Palner, Mikael, Janfelt, Christian
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 14 C-labelled Cimbi-36 and imaged by autoradiography. Finally, PET images were acquired from an animal dosed with 11 C-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-HT 2A and 5-HT 2C 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.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-021-01592-2