Debiopharm International SA, Chemin Messidor 5-7, 1002 Lausanne, Switzerland.
ImaBiotech, Parc Eurasanté, 152 rue du Docteur Yersin, 59120 Loos, France.
Anal Chem. 2022 Sep 13;94(36):12333-12341. doi: 10.1021/acs.analchem.2c00943. Epub 2022 Aug 30.
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.
由于肿瘤非常异质，因此研究抗癌药物在肿瘤不同组织学区域的渗透和浓度对于评估疗效、改善药代动力学/药效学（PK/PD）关系评估以及确认剂量方案的充分性至关重要。定量质谱成像（QMSI）可用于确定药物、代谢物和生物标志物在组织中的分布，以支持在单次实验中快速准确地评估药物的疗效和安全性。QMSI 应用于凋亡蛋白抑制剂拮抗剂 xevinapant（Debio 1143）在可切除头颈部鳞状细胞癌（SCCHN）患者术前机会窗（WoO）研究中。肿瘤被分离，立即冷冻并切片，然后通过基质辅助激光解吸电离（MALDI）成像生成药物的分子分布。此外，在与用于 QMSI 的切片相邻的染色切片上识别出不同的组织学区域（肿瘤、上皮、唾液腺、肌肉、神经和血管），从而进行了特定的定量分析，该定量分析整合了肿瘤异质性的生物学特征。这种创新方法可以突出 xevinapant 对肿瘤组织的高亲和力。
