Oral Sessions (Day1, Day2, Day3)
Poster Presentations
(Day1, Day2, Day3)
Oral Sessions
- Day 3, May 17(Fri.) 15:05-15:25 Room B (102)
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3B-O2-1505 PDF
Development of Detection Method for Antisense Oligonucleotide and Its Metabolites in Mouse Tissue by Imaging Mass Spectrometry
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.