title: A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-ContainingT1-Shortening Contrast Agent.
abstract: Responsive magnetic resonance imaging (MRI) contrast agents, those that change their relaxivity according to environmental stimuli, have promise as next generation imaging probes in medicine. While several of these are known based on covalent modification of the contrast agents, fewer are known based on controlling non-covalent interactions. We demonstrate here accentuated relaxivity of aT1-shortening contrast agent, Gd-DOTP5-based on non-covalent, hydrogen bonding of Gd-DOTP5-with a novel fluorous amphiphile. By contrast to the phosphonate-containing Gd-DOTP5-system, the relaxivity of the analogous clinically approved contrast agent, Gd-DOTA-is unaffected by the same fluorous amphiphile under similar conditions. Mechanistic studies show that placing the fluorous amphiphile in proximity of the gadolinium center in Gd-DOTP5-caused an increase in τm(bound-water residence lifetime or the inverse of water exchange rate, τm= 1/kex) and an increase in τR(rotational correlation time), with τRbeing the factor driving enhanced relaxivity. Further, these effects were not observed when Gd-DOTA-was treated with the same fluorous amphiphile. Thus, Gd-DOTP5-and Gd-DOTA-respond to the fluorous amphiphile differently, presumably because the former binds to the amphiphile with higher affinity. (DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraphosphonic acid; DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid).
authors.affiliation: Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, Los Angeles, California 90089-1661.
authors.forename: Xinping
authors.initials: X
authors.lastname: Wu
authors.affiliation: Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, Los Angeles, California 90089-1661.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Dawsey
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202.
authors.forename: Buddhima N
authors.initials: BN
authors.lastname: Siriwardena-Mahanama
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Allen
authors.affiliation: Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, Los Angeles, California 90089-1661.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Williams
keywords: DOTP; Fluoroakyl Groups; Gadolinium; MRI Contrast; T1