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 a 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 (L1) 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 (r1p = 6.99 mM−1 s−1, 24 MHz, 35 °C ± 0.1) than that of [Gd(DOTA)(H2O)]− (r1p = 3.56 mM−1 s−1, 20 MHz, 39 °C, pH 7.3) and [Gd(DO3A)(H2O)2] (r1p = 4.8 mM−1 s−1, 20 MHz, 40 °C) is attributed to the nature of the glucose-6-phosphate pendant arm. The longitudinal relaxivity of the complex in the presence of β-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 r2p/r1p ratio of 1.01 indicates that it is a T1-weighted contrast agent.

Graphical abstractA new gadolinium(III) complex of glucose-6-phosphate conjugated DO3A and its longitudinal and transverse relaxivities (6.99 and 7.02 mM−1 s−1, respectively) and longitudinal relaxivity in the presence of β-cyclodextrin (r1p = 9.62 mM−1 s−1) are reported. The r2p/r1p ratio of 1.01 indicates that it is a T1-weighted contrast agent.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of Gd(III) complex of glucose-6-phosphate conjugated DO3A is reported. ► The complex exhibits longitudinal relaxivity of 6.99 mM−1 s−1. ► The transverse relaxivity of the complex is 7.02 mM−1 s−1. ► r2p/r1p ratio of 1.01 indicates that the complex is a T1-weighted contrast agent. ► The longitudinal relaxivity in the presence of β-cyclodextrin is 9.62 mM−1 s−1.