Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

Abstract

The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487). The heterogeneous drug penetration in the tumors is evident from the MALDI imaging results and from the images analysis. The differences between the various models do not always relate to significant changes in drug content in tumor homogenate examined by classical HPLC analysis. The specificity of the method clarifies the heterogeneity of the drug distribution that is analyzed from a quantitative point of view too, highlighting how marked are the variations of paclitaxel amounts in different part of solid tumors.

Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib Penetration into Liver Metastases of Gastrointestinal Stromal Tumors

“…The observed apparent lack of drug also confirms the clinical practice for GIST patients with liver metastases that the best treatment option is a multidisciplinary one with continued TKI drug therapy and possibly surgical intervention (37). This result based on a small cohort of patient-derived tissues is in line with results from several MALDI-qMSI mouse studies on various chemotherapeutic drug agents in different cell line-based and patient-derived xenograft models (18,19,21,(38)(39)(40).…”

Predictive value of two polymorphisms in ABCB1, rs1045642 and rs1128503, in prognosis following taxane-containing chemotherapy: A meta-analysis

“…There are differences in the genetic and biological characteristics, clinical progression pattern, therapeutic responses, and prognoses among different tumor types; the distribution of paclitaxel in different tumors is also different [38]. Sensitivity analysis revealed that the study by Li et al [21] was a source of statistical heterogeneity.…”

Heterogeneous distribution of alectinib in neuroblastoma xenografts revealed by matrix‐assisted laser desorption ionization mass spectrometry imaging: a pilot study

“…We then sorted out the ion signal intensities of alectinib from tumours before and after normalization with IS and evaluated the quantitative properties of the intensity data by comparing the results of LC‐MS/MS concurrently. Although the ion intensities of drugs and endogenous components from tissues have been related to LC‐MS/MS in previous reports (Reyzer et al, ; Burnum et al, ; Hankin and Murphy, ; Koeniger et al, ), comparison of ion intensity data from anti‐cancer drugs using whole tumour slices before and after normalization with IS has not previously been attempted (Giordano et al, ).…”