title: The significance of microscopic mass spectrometry with high resolution in the visualisation of drug distribution.
abstract: The visualisation and quantitative analysis of the native drug distribution in a pre-clinical or clinical setting are desirable for evaluating drug effects and optimising drug design. Here, using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS) with enhanced resolution and sensitivity, we compared the distribution of a paclitaxel (PTX)-incorporating micelle (NK105) with that of PTX alone after injection into tumour-bearing mice. We demonstrated optically and quantitatively that NK105 delivered more PTX to the tumour, including the centre of the tumour, while delivering less PTX to normal neural tissue, compared with injection with PTX alone. NK105 treatment yielded a greater antitumour effect and less neural toxicity in mice than did PTX treatment. The use of high-resolution MALDI-IMS may be an innovative approach for pharmacological evaluation and drug design support.
authors.affiliation: Division of Therapeutics Development, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasunaga
authors.forename: Masaru
authors.initials: M
authors.lastname: Furuta
authors.forename: Koretsugu
authors.initials: K
authors.lastname: Ogata
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Koga
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Misato
authors.initials: M
authors.lastname: Takigahira
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008853:Microscopy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014018:Tissue Distribution; D047368:Tumor Burden
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel