Purpose:To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz-TTDA)] 2-[(4s)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecandioic acid] 2-designed for use as a hepatobiliary MR contrast agent. Materials and Methods:MR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5-T scanner. Sequential multislice T1-weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25°) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz-TTDA)] 2-in study groups (N ϭ 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA) 2-in control groups (N ϭ 12). Similar protocols of MR imaging with additional T2-weighted images were used for the rats with implanted HCC in both study and control groups (N ϭ 12, in each group). MR images were analyzed to evaluate the time-enhancement change (% increase of signal-to-noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver-lesion contrast-to-noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done. Results:The liver enhancement in normal rats reached a plateau 5-50 minutes after injection of [Gd(Bz-TTDA)] 2-, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz-TTDA)] 2-was significantly higher than with Gd-DTPA. The efficacy of tumor characterization with injection of [Gd(Bz-TTDA)]2-was similar to that of Gd-DTPA at the early dynamic phase of the contrast study. However, the liver-lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz-TTDA)] 2-in mice was 7.5 mmol/kg. Conclusion:The preliminary results in this animal study indicated that [Gd(Bz-TTDA)] 2-has the potential of becoming a reliable liver MR contrast agent.
Dynamic contrast-enhanced magnetic resonance angiography (DCE-MRA) is a good modality for the diagnosis of vascular diseases. Contrast agents that produce higher and longer enhancement in vessels are highly valued. The complex of gadolinium with (R,S)-4-carboxy-5,9,12-tris(carboxymethyl)-l-phenyl-2-oxa-5,9,12-triazatridecan-14-oic acid (Gd-TTDA-BOM) possesses a benzyloxymethyl group in the ligand TTDA-BOM with the capability of raising lipophilicity. The Gd-TTDA-BOM complex expresses higher and longer enhancement in mouse liver than that of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) because of its faster water exchange rate, higher reorientation time, and higher lipophilicity. Phantom studies have shown that Gd-TTDA-BOM has expressed with higher a±nity to human serum albumin (HSA) than Gd-DTPA. In general, these characteristics might provide an advantage for vascular imaging. To verify this in vivo, a 3T MR scanner was used to investigate the signal enhancement in the aorta of normal rats by DCE-MRA after the bolus injection of Gd-TTDA-BOM and compared this with the injection of Gd-DTPA. Gd-TTDA-BOM expressed higher and longer signal enhancement in the aorta than Gd-DTPA. These results suggest that Gd-TTDA-BOM could provide better image quality than Gd-DTPA as an enhancement agent in DCE-MRA.
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