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. 2014 Dec 1:168:177-183.
doi: 10.1016/j.jfluchem.2014.09.018.

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T1-Shortening Contrast Agent

Xinping Wu  1 , Anna C Dawsey  1 , Buddhima N Siriwardena-Mahanama  2 , Matthew J Allen  2 , Travis J Williams  1
Affiliations

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T1-Shortening Contrast Agent

Xinping Wu et al. J Fluor Chem. .

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 a T1-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 τ m (bound-water residence lifetime or the inverse of water exchange rate, τ m = 1/kex) and an increase in τ R (rotational correlation time), with τ R being 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).

Keywords: DOTP; Fluoroakyl Groups; Gadolinium; MRI Contrast; T1.

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Figures

Figure 1
Figure 1
Molecular structures of gadolinium-containing contrast agents Gd-DOTP5− and Gd-DOTA− and fluorous amphiphile (1).
Figure 2
Figure 2
Stacked plot of EPR spectra of Gd-DOTP5− at 9.34 MHz, 25 °C.
Figure 3
Figure 3
19F-NMR of an aqueous solution of 1 before (top) and after (bottom) the addition of Gd-DOTP5−.
Scheme 1
Scheme 1
A possible interaction between Gd-DOTP5− and fluorous amphiphile 1.
See this image and copyright information in PMC

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