A new potential contrast agent for magnetic resonance imaging: Synthesis and relaxivity studies of a gadolinium(III) complex of glucose-6-phosphate conjugated 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid

Synthesis and longitudinal and transverse relaxivities of gadolinium(III) complex, [Gd(DO3A-Pr-Glu-6-phos)(H2O)(2)] (4), of glucose-6-phosphate conjugated DO3A (DO3A-Pr-Glu-6-phos = 10-(3-(glucose-6-phosphate)oxypropyl)-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane and DO3A = 1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid) are reported. DO3A-Pr-Glu-6-phos (L-1) is synthesized by the reaction of bromopropane appended DO3A (3) with glucose-6-phosphate at room temperature. The magnetic moment of 4 is 7.49 BM, which is close to that of the free gadolinium(III) ion. The X- and Q-band epr spectra of 4 at LNT show a broad band with g-values of 2.167 and 2.033, respectively. The higher longitudinal relaxivity of 4 (r(1p) = 6.99 mM(-1) s(-1), 24 MHz, 35 degrees C +/- 0.1) than that of [Gd(DOTA)(H2O)](-)(r(1p) = 3.56 mM(-1) s(-1), 20 MHz, 39 degrees C, pH 7.3) and [Gd(DO3A)(H2O)(2)] (r(1p) = 4.8 mM(-1) s(-1), 20 MHz, 40 degrees C) is attributed to the nature of the glucose-6-phosphate pendant arm. The longitudinal relaxivity of the complex in the presence of p-cyclodextrin increases to 9.62 mM(-1) s(-1) due to the formation of the inclusion complex. The transverse relaxivity of 4 is 7.02 mM(-1) s(-1) and the r(2p)/r(1p) ratio of 1.01 indicates that it is a T-1-weighted contrast agent. (C) 2012 Elsevier Ltd. All rights reserved.