title: Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging.
abstract: The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487). The heterogeneous drug penetration in the tumors is evident from the MALDI imaging results and from the images analysis. The differences between the various models do not always relate to significant changes in drug content in tumor homogenate examined by classical HPLC analysis. The specificity of the method clarifies the heterogeneity of the drug distribution that is analyzed from a quantitative point of view too, highlighting how marked are the variations of paclitaxel amounts in different part of solid tumors.
authors.affiliation: Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giordano
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zucchetti
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Decio
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cesca
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fuso Nerini
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Maiezza
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Simonetta Andrea
authors.initials: SA
authors.lastname: Licandro
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Frapolli
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: D'Incalci
authors.initials: D
authors.lastname: Maurizio
authors.affiliation: Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Davoli
authors.affiliation: Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milan, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Morosi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel