Cryo-sectioning of mice for whole-body imaging of drugs and metabolites with desorption electrospray ionization mass spectrometry imaging - a simplified approach

摘要

A method is presented for whole-body imaging of drugs and metabolites in mice with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). Unlike most previous approaches to whole-body imaging which are based on cryo-sectioning using a cryo-macrotome, the presented approach is based on use of the cryo-microtome which is found in any histology lab. The tissue sections are collected on tape which is analyzed directly by DESI-MSI. The method is demonstrated on mice which have been dosed intraperitoneally with the antidepressive drug amitriptyline. By combining full-scan detection with the more selective and sensitive MS/MS detection, a number of endogenous compounds (lipids) were imaged simultaneously with the drug and one of its metabolites. The sensitivity of this approach allowed for imaging of drug and the metabolite in a mouse dosed with 2.7 mg amitriptyline per kg bodyweight which is comparable to the normal prescribed human dose. The simultaneous imaging of endogenous and exogenous compounds facilitates registration of the drug images to certain organs in the body by colored-overlay of the two types of images. The method represents a relatively low-cost approach to simple, sensitive and highly selective whole-body imaging in drug distribution and metabolism studies.