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.