Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers

Abstract

Mass spectrometry imaging (MSI) visualizes molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labeling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic pulmonary surfactants were imaged from distributions of intact and metabolic products of an added tracer, universally 13 C-labeled dipalmitoyl PC (U 13 C-DPPC). The parenchymal distributions of newly synthesized PC species were also imaged from incorporations of methyl -D 9 -choline. This dual labeling strategy demonstrated both lack of inhibition of endogenous PC synthesis by exogenous surfactant and location of acyl chain remodeling processes acting on the U 13 C-DPPC-labeled surfactant, leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events will greatly enhance our understanding of lipid metabolism in diverse tissues and has potential application to both clinical and experimental studies.

Structural amyloid plaque polymorphism is associated with distinct lipid accumulations revealed by trapped ion mobility mass spectrometry imaging

“…Based on our results, it is clear that in order to truly delineate spatial lipid dynamics, kinetic studies of lipid accumulation in Aβ proximity might be needed. Indeed, such approaches have been previously utilized, for instance, to follow surfactant metabolism in the lung (Ellis et al, 2021). Further, our lab recently utilized such a kinetic approach, in an imaging stable isotope labeling kinetic study (iSILK), where we followed Aβ peptide deposition during Aβ plaque maturation (Michno et al, 2021).…”

Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics

“…While NanoSIMS imaging provides outstanding data on nanoscopic isotope enrichment, one challenge of the technique is the limited molecular information retrievable, permitting analysis of intact peptides and proteins. This is something that can be achieved with matrix-assisted laser desorption/ionization MS-based IMS (MALDI-IMS), which has been successfully demonstrated for monitoring spatial enrichment and metabolization of intraperitoneally injected, stable isotope-labeled drug candidates (26) or intranasally instilled and intraperitoneally injected stable isotope-labeled phospholipids (27). Most importantly, MALDI-IMS allows for comprehensive, chemically specific A peptide imaging of A pathology in AD mouse models (10,28) and in postmortem human AD brain tissue (29,30).…”

Metabolomics of Esophageal Squamous Cell Carcinoma Tissues: Potential Biomarkers for Diagnosis and Promising Targets for Therapy

“…Metabolomics is the omics of simultaneous quantitative analysis of comprehensive profiles of metabolites in living systems, mainly using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), two common analytical techniques, for the analysis of findings in urine, plasma, or tissue. Characterization of small molecules, especially tissue analysis (especially valuable in the context of heterogeneous tissues such as the brain and cancer), can yield unambiguous biochemical information about disease mechanisms and thus provide new insights into diseaseaffected cell signaling pathways, generating new diagnostic biomarkers and new therapeutic approaches, maybe the most powerful way to study local and specific stimulus responses and pathogenesis today, and is now widely used in biomedicine, drug research, and other fields [8][9][10][11][12]. It is generally known that a distinctive feature in the development of malignant tumors is the alteration of metabolic processes and metabolic reprogramming, which is considered to be a new hallmark of cancer [13].…”