日本質量分析学会 第67回質量分析総合討論会

Abstract

Oral Sessions

Day 3, May 17(Fri.) 15:05-15:25 Room B (102)

Development of Detection Method for Antisense Oligonucleotide and Its Metabolites in Mouse Tissue by Imaging Mass Spectrometry

(1Otsuka Pharm, 2Osaka Univ., 3NIBIOHN)
oHiroyuki Yokoi1,2, Yuya Kasahara3, Satoshi Obika2,3, Takefumi Doi2, Haruhiko Kamada3

Oligonucleotide therapeutics are currently receiving great attention as next-generation pharmaceuticals. But its pharmacokinetic evaluation methods are still not sufficient, and in particular, more tools are needed to evaluate the tissue distribution of administered drugs and their metabolites.
MALDI-IMS was a breakthrough technique for localizing biomolecules directly in tissue sections. The advantage of MALDI-IMS is that it can localize multiple molecules in tissue sections simultaneously and label-free. This technique has been applied to the detection of administered drugs and their metabolites in tissue sections.
In this study we focused on antisense oligonucleotides, and developed a MALDI-IMS-based detection method to clarify the tissue distribution of antisense oligonucleotides and their metabolites. As a model antisense oligonucleotide, we used an antisense oligonucleotide containing locked nucleic acids (LNA-A).
Analysis of LNA-A-treated mouse livers and kidneys were performed using the developed method. In the liver sections, MALDI-IMS revealed that LNA-A was uniformly distributed. In the kidneys sections, MALDI-IMS revealed that LNA-A localized in a portion presumed to be the renal cortex. We also obtained information on LNA-A metabolites, which showed the same distribution profile as LNA-A in livers and kidneys.