Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Tumor Distribution by Quantitative Mass Spectrometry Imaging of the Inhibitor of Apoptosis Protein Antagonist Xevinapant in Patients with Resectable Squamous Cell Carcinoma of the Head and Neck (EudraCT Number: 2014-004655-31)
Ist Teil von
Analytical chemistry (Washington), 2022-09, Vol.94 (36), p.12333-12341
Ort / Verlag
Washington: American Chemical Society
Erscheinungsjahr
2022
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
As tumors are very heterogeneous, investigating the penetration and concentration of an anticancer drug in different histological regions of a tumor is key to evaluate the efficacy, to improve the pharmacokinetics/pharmacodynamics (PK/PD) relationship evaluation, and to confirm the adequacy of the dose regimen. Quantitative mass spectrometry imaging (QMSI) allows for the determination of the tissue distribution of drugs, metabolites, and biomarkers to support quick and precise evaluation of drug efficacy and safety in a single experiment. QMSI was applied in a preoperative window-of-opportunity (WoO) study of the inhibitor of apoptosis protein antagonist xevinapant (Debio 1143) in patients with resectable squamous cell carcinoma of the head and neck (SCCHN). Tumors were isolated, immediately snap-frozen, and sectioned, and then, the molecular distribution of the drug was generated by matrix-assisted laser desorption ionization (MALDI) imaging. Additionally, the different histological regions (tumor, epithelium, salivary glands, muscle, nerve, and blood vessels) were identified on stained sections adjacent to the ones used for QMSI, leading to a specific quantification integrating the biological characterization of the tumor heterogeneity. This innovative approach allowed one to highlight the high affinity of xevinapant for the tumor tissues.