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Heterogeneous distribution of alectinib in neuroblastoma xenografts revealed by matrix‐assisted laser desorption ionization mass spectrometry imaging: a pilot study
Author(s) -
Ryu Shoraku,
Hayashi Mitsuhiro,
Aikawa Hiroaki,
Okamoto Isamu,
Fujiwara Yasuhiro,
Hamada Akinobu
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14067
Subject(s) - alectinib , chemistry , alk inhibitor , neuroblastoma , anaplastic lymphoma kinase , cancer research , pathology , medicine , biology , cell culture , genetics , malignant pleural effusion , lung cancer
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 .