Gadolinium Complex of 1,4,7,10-Tetraazacyclo­dodecane-1,4,7-trisacetic Acid (DO3A)–Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclo­dodecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a <i>T</i>₁ hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high <i>r</i>₁ relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging

Regions of activation in control subjects compared to the lead-exposed subjects from between-group analysis during 2-back task at P<0.05, FWE-corrected for multiple comparisons.

<p>C = center, L = left, R = right.</p

Within group analysis of 2-back task.

<p>One-sample t-test group comparison in the control group (a) and in the lead-exposed subject group (b) (P<0.05, FWE-corrected for multiple comparison).</p

Between group analysis of 2-back task.

<p>The brain areas, which activated in control subjects compared to the lead-exposed subjects from between group analysis of 2-back task. Statistics correspond to an FWE rate correction of P<0.05 estimated using Monte Carlo simulations.</p

Regions of activation from within-group analysis during 2-back task at P<0.05, FWE-corrected for multiple comparisons in control group.

<p>C = center, L = left, R = right.</p

Demographic, clinical, and laboratory characteristics of study subjects.

<p>Mean ± SD, *:GM (range); in this case statistical significance was tested with log-transformed variables.</p

Multiple regression analyses for BOLD signal changes with log blood lead concentration as a predictor.

<p>* P<0.05.</p

Correlation between BOLD signal change and 2-back task performance (response accuracy).

<p>Percentage BOLD signal change in the left DLPFC (a) and right IPC (b) showed positive correlation with response accuracy in control subjects, while such trend was no longer showed in lead-exposed subjects (* : P<0.05, ** : P<0.01).</p

BOLD signal changes for N-back working memory task performance.

<p>The difference in 2-back task accuracy between lead-exposed subjects (oblique line) and control subjects was statistically significant (P<0.05, Student’s t-test), except for 1-back task accuracy.</p

The N-back working memory paradigm.

<p>In the 0-back condition, participants were asked to press a button if a specific target letter “” appeared. In the N-back (N is 1 or 2) condition, they were asked to respond when a letter matched one that had been presented N letters before the present letter.</p