title: Dendritic PARACEST contrast agents for magnetic resonance imaging.
abstract: MRI contrast agents based on chemical exchange-dependent saturation transfer (CEST), such as Yb(III)DOTAM complexes, are highly suitable for pH mapping. In this paper, the synthesis of Yb(III)DOTAM-functionalized poly(propylene imine) dendrimers is described. The applicability of these dendritic PARACEST MRI agents for pH mapping has been evaluated on a 7 T NMR spectrometer and on a 3 T clinical MRI scanner. As expected, based on the different numbers of exchangeable amide protons, the lowest detectable concentration of the first and third generation dendritic PARACEST agents is by a respective factor of about 4 and 16 lower than that of a mononuclear reference complex. The pH dependence of the CEST effect observed for these compounds depends on the generation of the poly(propylene imine) dendrimer. Upon going to higher generations of the Yb(III)DOTAM-terminated dendrimer, a shift of the maximum CEST effect towards lower pH values was observed. This allows for a fine-tuning of the responsive pH region by varying the dendritic framework.
authors.affiliation: Philips Research Europe, High Tech Campus 11, 5656 AE Eindhoven, The Netherlands. jeroen.pikkemaat@philips.com
authors.forename: J A
authors.initials: JA
authors.lastname: Pikkemaat
authors.forename: R T
authors.initials: RT
authors.lastname: Wegh
authors.forename: R
authors.initials: R
authors.lastname: Lamerichs
authors.forename: R A
authors.initials: RA
authors.lastname: van de Molengraaf
authors.forename: S
authors.initials: S
authors.lastname: Langereis
authors.forename: D
authors.initials: D
authors.lastname: Burdinski
authors.forename: A Y F
authors.initials: AY
authors.lastname: Raymond
authors.forename: H M
authors.initials: HM
authors.lastname: Janssen
authors.forename: B F M
authors.initials: BF
authors.lastname: de Waal
authors.forename: N P
authors.initials: NP
authors.lastname: Willard
authors.forename: E W
authors.initials: EW
authors.lastname: Meijer
authors.forename: H
authors.initials: H
authors.lastname: Grüll
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D009942:Organometallic Compounds; D011126:Polypropylenes; C443641:poly(propyleneimine); C101405:ytterbium-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid