title: Monitoring therapeutic monoclonal antibodies in brain tumor.
abstract: Bevacizumab induces normalization of abnormal blood vessels, making them less leaky. By binding to vascular endothelial growth factor, it indirectly attacks the vascular tumor mass. The optimal delivery of targeted therapies including monoclonal antibodies or anti-angiogenesis drugs to the target tissue highly depends on the blood-brain barrier permeability. It is therefore critical to investigate how drugs effectively reach the tumor. In situ investigation of drug distribution could provide a better understanding of pharmacological agent action and optimize chemotherapies for solid tumors. We developed an imaging method coupled to protein identification using matrix-assisted laser desorption/ionization mass spectrometry. This approach monitored bevacizumab distribution within the brain structures, and especially within the tumor, without any labeling.
authors.affiliation: a Aix-Marseille Université Inserm ; CRO2 UMR S-911; Marseille , France.
authors.forename: Rima
authors.initials: R
authors.lastname: Ait-Belkacem
authors.forename: Caroline
authors.initials: C
authors.lastname: Berenguer
authors.forename: Claude
authors.initials: C
authors.lastname: Villard
authors.forename: L'Houcine
authors.initials: L
authors.lastname: Ouafik
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Alain
authors.initials: A
authors.lastname: Beck
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.forename: Daniel
authors.initials: D
authors.lastname: Lafitte
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068258:Bevacizumab; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008819:Mice, Nude; D000069455:Palivizumab; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069455:Palivizumab
keywords: 5 DAN, 1; 5-diaminonaphtalene; BBB, blood-brain barrier; CRC, metastatic colorectal cancer; CSF, cerebrospinal fluid; 1; EMA, European Medicines Agency; FDA, Food and Drug Administration; GBM, glioblastoma multiforme; IMS, imaging mass spectrometry; ISD, in-source decay; ITO, indium tin oxide; LC-MS/MS, liquid chromatography coupled to tandem mass spectrometry; MALDI imaging mass spectrometry; MALDI, matrix-assisted laser desorption/ionization; NSCLC, non-small cell lung cancer; RMS, root mean square; RP-HPLC, reversed phase high-performance liquid chromatography; TOF, time of flight; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; VH, variable domain of the heavy chain; VL, variable domain of the light chain; WHO, world health organization; bevacizumab; glioblastoma multiforme; mAbs, monoclonal antibodies; monoclonal antibodies; pE, pyroglutamate; palivizumab; top down in source decay