Jacobsen Sophie C, Speth Nikolaj R, Xiong Mengfei, Herth Matthias M, Kristensen Jesper L, Palner Mikael, Janfelt Christian
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Neurobiology Research Unit, Copenhagen University Hospital, Blegdamsvej 9, 2200, Copenhagen, Denmark.
Mol Imaging Biol. 2021 Oct;23(5):676-685. doi: 10.1007/s11307-021-01592-2. Epub 2021 Mar 2.
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.
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-labelled Cimbi-36 and imaged by autoradiography. Finally, PET images were acquired from an animal dosed with C-labelled Cimbi-36.
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 and 5-HT 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.
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.
本研究展示了解吸电喷雾电离质谱成像（DESI-MSI）在脑组织中对正电子发射断层扫描（PET）示踪剂化合物Cimbi-36进行成像的应用，并将DESI-MSI成像与放射自显影成像和PET成像进行比较。
给大鼠腹腔注射3mg/kg的Cimbi-36，并在注射后5、10、15、30、60和120分钟时实施安乐死。取出大脑，冷冻并切片，矢状切片在正离子模式下通过DESI-MSI进行成像。此外，将未给药动物的脑切片与碳标记的Cimbi-36一起孵育，并通过放射自显影进行成像。最后，从注射了碳标记的Cimbi-36的动物获取PET图像。
矢状脑切片的DESI-MSI图像和放射自显影图像显示Cimbi-36的分布相似，在额叶皮质和脉络丛中丰度增加，这些区域5-羟色胺（5-HT）和5-HT受体含量较高。PET图像也显示皮质中的丰度增加，但空间分辨率明显低于DESI-MSI和放射自显影。DESI-MSI结果显示脑组织中Cimbi-36的丰度在15分钟前增加，之后丰度下降。在t = 120分钟时仍可清晰检测到PET示踪剂。对肾脏的类似成像显示Cimbi-36的丰度在30分钟时达到峰值。通过定量DESI-MSI对t = 15分钟的脑切片中的Cimbi-36进行定量，得出皮质中的组织浓度为19.8μg/g，小脑中为15.4μg/g，全脑中为12.5μg/g。
来自体内给药实验的DESI成像显示PET示踪剂的分布与体外孵育实验的放射自显影结果非常相似，表明所获得的结果代表了与大脑中某些受体的实际结合。建议将DESI-MSI作为一种经济高效的筛选工具，其不依赖于化合物的标记。
