title: Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents.
abstract: A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.
authors.affiliation: Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.|Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.
authors.forename: Mojmír
authors.initials: M
authors.lastname: Suchý
authors.affiliation: Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Milne
authors.affiliation: Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.
authors.forename: Adam A H
authors.initials: AA
authors.lastname: Elmehriki
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.
authors.forename: Nevin
authors.initials: N
authors.lastname: McVicar
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.
authors.forename: Alex X
authors.initials: AX
authors.lastname: Li
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Bartha
authors.affiliation: Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.|Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario , London, Ontario N6A 5B7, Canada.
authors.forename: Robert H E
authors.initials: RH
authors.lastname: Hudson
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D003287:Contrast Media / Q000138:chemical synthesis* / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D007668:Kidney / Q000033:anatomy & histology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000633:toxicity*; D013932:Thulium / Q000737:chemistry*
chemical_list: C533989:(1,4,7,10-tetrakis((N-(1H-imidazol-2-yl)carbamoyl)methyl)-1,4,7,10-tetraazacyclododecane)thulium(III); D002264:Carboxylic Acids; D003287:Contrast Media; D009942:Organometallic Compounds; D001224:Aspartic Acid; D013932:Thulium