Heterogeneity in brain tumors can result in variable drug distribution and possibly drug response; however, there are no readily accessible means to obtain regional pharmacokinetic (PK)/pharmacodynamic (PD) information in preclinical tumor models that typically rely on average drug concentration measurements. On the basis of a novel serial brain tumor sectioning protocol, sensitive and robust methods were developed to characterize the intratumoral PK [liquid chromatography with tandem mass spectrometry detection (LC/MS/MS)] and PD (phosphorylated extracellular-signal-regulated kinase, antibody-based detection) of gefitinib in small amounts of glioblastoma tumor samples obtained from mice bearing intracerebral tumors administered 150 mg/kg of gefitinib. LC/MS/MS method was accurate (±15%) and precise (coefficient of variation ≤15%). For PD analysis, two antibody-based assay systems [enzyme-linked immunosorbent assay and meso scale discovery (MSD)] were compared and the more sensitive method (MSD) was selected. Gefitinib concentrations showed up to 2.4 ± 0.7-fold intratumoral variability in PK and 1.5 ± 0.20-fold variability in PD. The methods are sufficiently accessible and could be applied to other anticancer drugs and tumor models to obtain greater resolution of intratumoral PKs and PDs.

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乐备实是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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