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

Shoraku Ryu, Mitsuhiro Hayashi, Hiroaki Aikawa, Isamu Okamoto, Yasuhiro Fujiwara, Akinobu Hamada

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    14 Citations (Scopus)

    Abstract

    Background and Purpose: The penetration of the anaplastic lymphoma kinase (ALK) inhibitor alectinib in neuroblastomas and the relationship between alectinib and ALK expression are unknown. The aim of this study was to perform a quantitative investigation of the inter- and intra-tumoural distribution of alectinib in different neuroblastoma xenograft models using matrix-assisted laser desorption ionization MS imaging (MALDI-MSI). Experimental Approach: The distribution of alectinib in NB1 (ALK amplification) and SK-N-FI (ALK wild-type) xenograft tissues was analysed using MALDI-MSI. The abundance of alectinib in tumours and intra-tumoural areas was quantified using ion signal intensities from MALDI-MSI after normalization by correlation with LC-MS/MS. Key Results: The distribution of alectinib was heterogeneous in neuroblastomas. The penetration of alectinib was not significantly different between ALK amplification and ALK wide-type tissues using both LC-MS/MS concentrations and MSI intensities. Normalization with an internal standard increased the quantitative property of MSI by adjusting for the ion suppression effect. The distribution of alectinib in different intra-tumoural areas can alternatively be quantified from MS images by correlation with LC-MS/MS. Conclusion and Implications: The penetration of alectinib into tumour tissues may not be homogenous or influenced by ALK expression in the early period after single-dose administration. MALDI-MSI may prove to be a valuable pharmaceutical method for elucidating the mechanism of action of drugs by clarifying their microscopic distribution in heterogeneous tissues.

    Original languageEnglish
    Pages (from-to)29-37
    Number of pages9
    JournalBritish Journal of Pharmacology
    Volume175
    Issue number1
    DOIs
    Publication statusPublished - Jan 2018

    All Science Journal Classification (ASJC) codes

    • Pharmacology

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