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New Technology                                                                                                                                         71
























                             Acknowledgments This work was supported by the Funding Program for  World-Leading Innovative R&D on Science and Technology  (FIRST Program) (YM), Third Term Comprehensive Control  Research for Cancer from the Ministry of Health, Labour and  Welfare of Japan (YM), a Grant-in-Aid for Scientific Research on Priority Areas from the  Ministry of Education, Culture, Sports, Science and Technology,  the National Cancer Center Research and Development Fund  (YM and MY), the Kobayashi Foundation Research Grant for   Cancer Research (MY), and a Grant-in-Aid for Scientific Research from  the Japan Society for the Promotion of Science (MY). We thank  Mrs K. Shiina for her secretarial support.  Author contributions Y.M. de









                             17. Matsumura, Y. & Kataoka, K. Preclinical and clinical studies of
                               anticancer agentincorporating polymer micelles. Cancer Sci.
















                                  100, 572–579 (2009). 18. Matsumura, Y. & Maeda, H. A new concept for  macromolecular therapeutics in cancer chemotherapy:  mechanism of tumoritropic accumulation of proteins and the  antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986). 19. Duncan, R. Polymer conjugates as anticancer nanomedicines.  Nat. Rev. Cancer 6, 688–701 (2006). 20. Peer, D. et al. Nanocarriers as an emerging platform for  cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007). 21. Ibrahim, N. K. et al. Multicenter phase II trial of ABI-007, an  albumin-bound paclitaxel, in women with metastatic breast  cancer. J Clin Oncol. 23, 6019–26 (2005). 22. Johnson,D.H., Chang, A. Y.&Ettinger, D. S. Taxol (paclitaxel)  in the treatment of l























                                      generated using the product m/z 104.95 ion was used. The data were
                                    performed with the precursor m/z 854.45 ion, and the standard curve
                             terms of the gradient, acetonitrile was conducted at 50% (B) for the
                                  decreased back to 50% for 1.25 min. The PTX quantification was
                               first 1.5 min, increased to 100% for 0.25 min, and subsequently










                                        collected in triplicate experiments.  References   1. Chin, L. & Gray, J. W. Translating insights from the cancer  genome into clinical practice. Nature 452, 553–563 (2008).   2. Van Dort, M. E., Rehemtulla, A. & Ross, B. D. PET and SPECT  Imaging of Tumor Biology: New Approaches towards  Oncology Drug Discovery and Development. Curr. Comput.  Aided Drug Des. 4, 46–53 (2008).   3. Garrett, M. D. &Workman, P. Discovering novel  chemotherapeutic drugs for the third millennium. Eur. J.  Cancer 35, 2010–2030 (1999).   4. Abramson, R. G. et al. Complications of targeted drug  therapies for solid malignancies: manifestations and  mechanisms. AJR Am J Roentgenol. 200, 475–483 (2013).   5. Horak, C. E. et a





























         global w430×h280    MS/MS analysis of PTX (m/z 892.3) was performed with the CID function  of the quadruple ion trap cell on the Mass Microscope. The m/z 607.19  fragment ion was generated on the tissue. This ion was also observed for  the authentic PTX as the derivative and was used for MS/MS imaging of  the drug. The instrument conditions for MS/MS imaging were identical to  those used for the MS mapping described above, but the spatial  resolution was 15 µm, and the laser power was 50%. Female BALB/c nude mice (5 weeks old) and DBA/2N mice (8 weeks  old) were purchased from SLC Japan (Shizuoka, Japan). The nude  mice were inoculated subcutaneously in the flank with 1 × 10 6  BxPC3  cells. The length (L) and width (W) of the tu






                    New Technology           Animal model.  Antitumour activity.  Peripheral neuropathy.                     with tumour cells.  (ANOVA) with Tukey’  LC-MS.  70
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