title: 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors.
abstract: Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.
authors.affiliation: Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Giordano
authors.affiliation: Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Morosi
authors.affiliation: Neuroscience Department, Biology of Neurodegenerative Disorders Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Veglianese
authors.affiliation: Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: S A
authors.initials: SA
authors.lastname: Licandro
authors.affiliation: Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Frapolli
authors.affiliation: Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zucchetti
authors.affiliation: Chemistry Department, University of Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cappelletti
authors.affiliation: Chemistry Department, University of Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Falciola
authors.affiliation: Chemistry Department, University of Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Pifferi
authors.affiliation: Department of Molecular Biotechnology and Health Science, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Visentin
authors.affiliation: Oncology Department, Cancer Pharmacology Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Environmental Health Sciences Department, Mass Spectrometry Laboratory, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Davoli
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008654:Mesothelioma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014025:Titanium / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C009495:titanium dioxide; D014025:Titanium; D017239:Paclitaxel