Abstract: FR-PO0684
In Situ Analysis of Drug and Metabolite Distribution in a Three-Dimensional In Vivo Cyst Model of ADPKD Using Desorption Electrospray Ionization-Mass Spectrometry (DESI-MS)
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Schueler, Jan, Universitat Regensburg, Regensburg, BY, Germany
- Heckscher, Simon, Universitat Regensburg, Regensburg, BY, Germany
- Groß, Verena, Klinikum St Elisabeth Straubing GmbH, Straubing, BY, Germany
- May, Matthias, Klinikum St Elisabeth Straubing GmbH, Straubing, BY, Germany
- Nuebel, Barbara, Universitatsklinikum Erlangen, Erlangen, BY, Germany
- Wullich, Bernd, Universitatsklinikum Erlangen, Erlangen, BY, Germany
- Buchholz, Bjoern, Universitat Regensburg, Regensburg, BY, Germany
- Werner, Jens M., Universitatsklinikum Regensburg, Regensburg, BY, Germany
- Jantsch, Jonathan, Universitat zu Koln, Cologne, NRW, Germany
- Gronwald, Wolfram, Universitat Regensburg, Regensburg, BY, Germany
- Takats, Zoltan, Universitat Regensburg, Regensburg, BY, Germany
- Oefner, Peter J., Universitat Regensburg, Regensburg, BY, Germany
- Schmidt, Katharina Maria, Universitatsklinikum Regensburg, Regensburg, BY, Germany
- Haerteis, Silke, Universitat Regensburg, Regensburg, BY, Germany
- Dettmer, Katja, Universitat Regensburg, Regensburg, BY, Germany
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. Recently, it has been demonstrated that human ADPKD kidney tissue can be cultured and analyzed for up to seven days on the chorioallantoic membrane (CAM), a three-dimensional in vivo model that holds promise as a platform for preclinical studies. Here, we demonstrate its usefulness in studying the absorption, distribution and metabolism of topically applied active substances by means of mass spectrometry imaging (MSI) using DESI for in-situ desorption and ionization in combination with a ultrahigh-resolution time-of-flight mass spectrometer.
Methods
Renal cyst tissue obtained from elective cyst nephrectomies was cultured for one week on the CAM. The tissue was treated daily by topical application of benzbromarone, a potential therapeutic agent for inhibiting cyst growth. One hour after the final treatment, the tissue was removed from the CAM, snap-frozen, and cryosectioned. The cryosections were first analyzed by DESI-MS, followed by histological examination of the same sections after H&E-staining.
Results
Renal cyst tissue was clearly identifiable in the MSI images and could be distinguished from the surrounding CAM tissue due to its distinct lipid and metabolite content. In addition, benzbromarone was successfully detected within the renal cyst tissue. The MSI images did not only reveal how benzbromarone penetrated the renal cyst tissue, but also its accumulation around the cyst epithelium. Furthermore, metabolites of benzbromarone and compounds associated with apoptotic processes were detected.
Conclusion
Using mass spectrometry imaging, we were able to convincingly demonstrate that the CAM model is suitable as a platform for drug testing in human tissue. MSI provided detailed insights into the behavior of the applied drug within the tissue, confirming not only tissue penetration by the active substance but also allowing characterization of its distribution, accumulation and metabolism.
Funding
- Government Support – Non-U.S.