Comparison of Gd-Bz-TTDA, Gd-EOB-DTPA, and Gd-BOPTA for dynamic MR imaging of the liver in rat models

Abstract

To evaluate the competitive potential of a new lipophilic paramagnetic complex, Gd-Bz-TTDA [4-benzyl-3,6,10-tri (carboxymethyl)-3,6,10-triazado-decanedioic acid] compared with two other commercially available MR hepatobiliary contrast agents, gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB-DTPA), dynamic MR imaging studies were performed on normal and hepatocellular carcinoma (HCC) rat models using a 1.5-Tesla MR scanner. The results indicate that normal rats that were injected with 0.1 mmol/kg Gd-Bz-TTDA showed significantly more intense and persistent liver enhancement than those that were injected with the same dose of Gd-EOB-DTPA or Gd-BOPTA. All of these agents showed similar enhancement patterns in the implanted HCC. The liver-lesion contrast-to-noise ratios were higher and more persistent in rats that were injected with Gd-Bz-TTDA. These results indicate that Gd-Bz-TTDA is comparable with the commercially available hepatobiliary agents, Gd-EOB-DTPA and Gd-BOPTA, and can result in more intense and prolonged liver enhancement while still providing better liver-lesion discrimination. These results warrant further large-scale studies.

Figure 1

Time‐enhancement changes in the livers of normal rats after the injection of 0.1 mmol/kg Gd‐Bz‐TTDA, Gd‐EOB‐DTPA, or Gd‐BOPTA on T1‐weighted images (mean ± standard deviation, n = 12 in each group).

Figure 2

Gd‐Bz‐TTDA, Gd‐EOB‐DTPA, and Gd‐BOPTA enhanced dynamic T1‐weighted TFE images in normal rats. A: Precontrast images. B: Arterial phase at 28 seconds. C: Venous phase at 70 seconds. D: Equilibrium phase at 126 seconds. E, F, G, and H: Hepatobiliary phase at 5–120 minutes. Gd‐Bz‐TTDA produced more intense enhancement in liver than the other two groups at 30, 60, and 120 minutes. Circle: reference standard.

Figure 3

Sequential T1‐weighted TFE images of a rat with implanted HCC before and after injection of 0.1 mmol/kg Gd‐Bz‐TTDA (A), Gd‐EOB‐DTPA (B), or Gd‐BOPTA (C). In the images recorded at 28 and 70 seconds, similar degrees of tumor enhancement are noted in each group. At 5 minutes, good liver‐to‐lesion differentiation is demonstrated in all three groups due to the intense liver enhancement and wash‐out of the tumor contrast agent. At 60 and 120 minutes, persistent and intense liver enhancement with better liver‐lesion contrast is noted following the injection of Gd‐Bz‐TTDA; however, only faint enhancement of the liver and noticeably less discrimination of the lesions are noted in the other two groups. The arrows indicate the tumor. (D) Cut surface of an autopsied specimen with liver HCC showing central necrosis (arrow head). (E) Histological specimen demonstrating poorly differentiated HCC, which consists of dark and light cells. Mitotic features and hypervascularity are also noted. (hematoxylin and eosin stain, original magnification 80×).

Figure 4

Percentage increase in liver‐lesion CNR in rats with HCC after injection of Gd‐Bz‐TTDA, Gd‐EOB‐DTPA, or Gd‐BOPTA (mean; n = 6 in each group; solid: solid part of tumor; necrotic: central necrotic part of the tumor).