Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract

Abstract

A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 47 hours, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated.

Gd3+-1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic-2-hydroxypropyl-β-cyclodextrin/Pluronic Polyrotaxane as a Long Circulating High Relaxivity MRI Contrast Agent

“…Relaxivity measurements (Figure ) of the monomeric and rotaxanated Gd 3+ agents gave r 1 values of 7.82 and 23.83 mM –1 s –1 per Gd chelate for Gd 3+ -DO3A-HPCD and Gd 3+ -DO3A-HPCD/Pluronic PR, respectively, at 1.5 T, 37 °C (8.46 and 34.08 mM –1 s –1 at 0.5 T, respectively, Supporting Information). The Gd 3+ -DO3A-HPCD r 1 relaxivity is in good agreement with the ionic relaxivity reported for other cyclodextrin monomeric contrast agents ([Gd 3+ -DOTA] 7 -β-CD, r 1 = 12.2 mM –1 s –1 at 1.5 T; [Gd 3+ -DTTA] 7 -β-CD, r 1 = 6.2 mM –1 s –1 at 9.4 T) and a dextran-DTPA derivative with a similar Gd 3+ content ( r 1 = 10.5 mM –1 s –1 at 0.25 T); a [Gd 3+ -DOTA] 8 -sucrose derivative (4.1 mM –1 s –1 ), all measured at 37 °C. The greater than 3-fold improvement in ionic relaxivity of the PR construct relative to the Gd 3+ -DO3A-HPCD monomer is attributed to the increased polymer rigidity imparted by rotaxanation as well as reduced rotational motion of the threaded, hydrogen-bonded nearest-neighbor cyclodextrin units.…”

“…28 Relaxivity measurements (Figure 2) of the monomeric and rotaxanated Gd 3+ agents gave r 1 values of 7.82 and 23.83 mM −1 s −1 per Gd chelate for Gd 3+ -DO3A-HPCD and Gd 3+ -DO3A-HPCD/Pluronic PR, respectively, at 1.5 T, 37 °C (8.46 and 34.08 mM −1 s −1 at 0.5 T, respectively, Supporting Information). The Gd 3+ -DO3A-HPCD r 1 relaxivity is in good agreement with the ionic relaxivity reported for other cyclodextrin monomeric contrast agents ([Gd 3+ -DOTA] 7 -β-CD, r 1 = 12.2 mM −1 s −1 at 1.5 T; 20 [Gd 3+ -DTTA] 7 -β-CD, r 1 = 6.2 mM −1 s −1 at 9.4 T 21 ) and a dextran-DTPA derivative with a similar Gd 3+ content (r 1 = 10.5 mM −1 s −1 at 0.25 T); 7 a [Gd 3+ -DOTA] 8 -sucrose derivative (4.1 mM −1 s −1 ), 29 all measured at 37 °C. The greater than 3-fold improvement in ionic relaxivity of the PR construct relative to the Gd 3+ -DO3A-HPCD monomer is attributed to the increased polymer rigidity imparted by rotaxanation as well as reduced rotational motion of the threaded, hydrogen-bonded nearest-neighbor cyclodextrin units.…”

A novel gamma GLM approach to MRI relaxometry comparisons

“…To date, there is no standard protocol for how to best design and analyze a relaxivity experiment . Similar problems have been addressed previously in UV‐Vis spectroscopy and liquid chromatography‐mass spectrometry (LC‐MS) through weighted least squares (WLS), which has also been applied on occasion to relaxivity . Although WLS is a potential solution, the GGLM approach proposed in this work is more flexible as it assigns weights empirically by an iterative reweighted least squares algorithm .…”

Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry

“…Accordingly D-ribose 11, on treatment with methanol and catalytic conc. sulfuric acid furnished the methyl ribofuranoside 12 (14), which on treatment with sodium hydride and phenylpropyl bromide 13 furnished 2,3,5-trisprotected methylribofuranoside, 14 (15). Compound 14 on treatment with HBr-AcOH (16) gave the corresponding ribosylbromide 15, which on reaction with dibenzyl phosphate 3 gave ribose-dibenzylphosphate 16.…”