TY - JOUR

T1 - Desorption Electrospray Ionization Mass Spectrometry Imaging of Cimbi-36, a 5-HT2A Receptor Agonist, with Direct Comparison to Autoradiography and Positron Emission Tomography

AU - Jacobsen, Sophie C.

AU - Speth, Nikolaj R.

AU - Xiong, Mengfei

AU - Herth, Matthias M.

AU - Kristensen, Jesper L.

AU - Palner, Mikael

AU - Janfelt, Christian

PY - 2021

Y1 - 2021

N2 - 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 C-14-labelled Cimbi-36 and imaged by autoradiography. Finally, PET images were acquired from an animal dosed with C-11-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 mu g/g in cortex, 15.4 mu g/g in cerebellum and 12.5 mu g/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.

AB - 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 C-14-labelled Cimbi-36 and imaged by autoradiography. Finally, PET images were acquired from an animal dosed with C-11-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 mu g/g in cortex, 15.4 mu g/g in cerebellum and 12.5 mu g/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.

KW - DESI-MSI

KW - PET ligands

KW - Rat brain

KW - Mass spectrometry imaging

KW - Autoradiography

KW - 5-HT2(A) receptor agonist

U2 - 10.1007/s11307-021-01592-2

DO - 10.1007/s11307-021-01592-2

M3 - Journal article

C2 - 33651266

VL - 23

SP - 676

EP - 685

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

ER -