High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni

Annika S Mokosch,Christoph G Grevelding,Bernhard Spengler,Simone Haeberlein,Stefanie Gerbig

doi:10.1007/s00216-021-03230-w

Abstract

Schistosoma mansoni is a parasitic flatworm causing schistosomiasis, an infectious disease affecting several hundred million people worldwide. Schistosomes live dioeciously, and upon pairing with the male, the female starts massive egg production, which causes pathology. Praziquantel (PZQ) is the only drug used, but it has an inherent risk of resistance development. Therefore, alternatives are needed. In the context of drug repurposing, the cancer drug imatinib was tested, showing high efficacy against S. mansoni in vitro. Besides the gonads, imatinib mainly affected the integrity of the intestine in males and females. In this study, we investigated the potential uptake and distribution of imatinib in adult schistosomes including its distribution kinetics. To this end, we applied for the first time atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) for drug imaging in paired S. mansoni. Our results indicate that imatinib was present in the esophagus and intestine of the male as early as 20 min after in vitro exposure, suggesting an oral uptake route. After one hour, the drug was also found inside the paired female. The detection of the main metabolite, N-desmethyl imatinib, indicated metabolization of the drug. Additionally, a marker signal for the female ovary was successfully applied to facilitate further conclusions regarding organ tropism of imatinib. Our results demonstrate that AP-SMALDI MSI is a useful method to study the uptake, tissue distribution, and metabolization of imatinib in S. mansoni. The results suggest using AP-SMALDI MSI also for investigating other antiparasitic compounds and their metabolites in schistosomes and other parasites.Graphical abstract

Highlights

Schistosomiasis is a disease caused by trematodes of the genus Schistosoma, with more than 200 million people affected and around 200,000 annual deaths globally
We have investigated imatinib distribution in cryosections of S. mansoni after refining the sample preparation protocol and applying high-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) (AP-SMALDI MSI)
Because single females are extremely thin, longitudinal sectioning required for AP-SMALDI MSI is difficult to achieve [27]

Summary

Introduction

Schistosomiasis is a disease caused by trematodes of the genus Schistosoma, with more than 200 million people affected and around 200,000 annual deaths globally. The female produces hundreds of eggs per day, which are released into the bloodstream of the final host, such as humans. The rest of the eggs, migrate via the bloodstream and get trapped in different organs such as the spleen and liver. These eggs cause granuloma formation and inflammatory processes, leading to liver fibrosis [6]. Praziquantel (PZQ) is used as the only available drug effective against all schistosome species relevant to humans [7]. There is no vaccine available, which alarmingly limits disease control [10, 11]

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Results

Conclusion