Newsletter Volume 39, Number 1, 2024


顔写真:Siyu Liu

Best Poster Award -comment from the winner-

Siyu Liu
Center of Excellence for Drug Metabolism, Pharmacokinetics and Modeling
Preclinical and Translational Sciences, Research
Takeda Pharmaceutical Company Limited

I’m deeply pleased and honored to receive the best poster award from expert professionals of the JSSX for our presentation entitled ‘Establishment of a workflow for spatial pharmacokinetics analysis using three-dimensional (3D) microscopic imaging data’. It’s our privilege to be recognized by the JSSX committee.

This work can be treated as a further step to interpret the microenvironment pharmacokinetic (PK) data from previous 3D microscopy imaging study, which won the best poster award last year [1]. It is observed that the administered antisense oligonucleotides (ASOs) are not uniformly distributed in the tissues. Therefore, spatial PK analysis is crucial for understanding the mechanism of tissue distribution as well as the relationship between PK and efficacy in microenvironment. In this study, we established a comprehensive workflow utilizing a concentrated Python platform for 3D spatial PK analysis of the whole mouse brain distribution data generated from light-sheet fluorescence microscopy (LSFM). It is noted that this platform will not only be limited to the ASO PK analysis but also could be applied to the microscopy imaging data of other modalities.

In the case study, we analyzed ASOs’ mice brain LSFM data after intracerebroventricular (ICV) or intravenous (IV) administrations. The results of the spatial PK analysis suggested: 1) Whole brain images were successfully analyzed by the established workflow to indicate regional (macro-) and parenchymal (micro-) PK insights. 2) Drug signal intensity per regional tissue volume could be quantified for brain regions of interest, which shared similar PK profile pattern to the LC-MS/MS macro-PK data. 3) Parenchyma intensity profiles demonstrated different parenchyma disposition patterns among different brain regions. 4) Parenchyma/Total intensity ratio suggested route-dependent and time-dependent but not region-dependent distribution from perivascular space to parenchymal space. 5) Potential distinct distribution patterns of ASOs after ICV versus IV. The workflow helped us to disclose the insights on the new modality brain distribution from the microscopy images. This platform will be extended to micro- and cellular based PKPD analysis in the future.

Finally, I would like to thank the co-coauthors Miyu Nakayama, Asahi Adachi, Syunsuke Yamamoto, Akihiko Goto and Shinji Iwasaki for their contributions to the study. I also thank our colleagues Xiaoxi Liu and Hisashi Fujita for providing the bioanalysis PK data as well as our former intern Kio Yagami for his efforts. Last but not least, I am grateful to all the DMPK&M colleagues at Takeda Pharmaceutical Co. Ltd. for their suggestions and comments.