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[钆(苯甲酰基 - TTDA)]²⁻作为肝胆系统磁共振成像潜在造影剂的评估:一项动物研究。

Evaluation of [Gd(Bz-TTDA)]2- as a potential contrast agent in MR imaging of the hepatobiliary system: an animal study.

作者信息

Hsu Jui-Sheng, Jaw Twei-Shiun, Liu Gin-Chung, Wang Yun-Ming, Chen Shih-Hsien, Kuo Yu-Ting, Jao Jo-Chi, Li Chun-Wei, Tsai Kun-Bow

机构信息

Department of Medical Imaging, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

J Magn Reson Imaging. 2004 Oct;20(4):632-9. doi: 10.1002/jmri.20151.

Abstract

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 degrees) 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 = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA)2- in control groups (N = 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 = 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.

摘要

目的

评估一种新型亲脂性顺磁性复合物[钆(苯甲酰基 - TTDA)]2 - [(4s)-4 - 苄基 - 3,6,10 - 三(羧甲基)-3,6,10 - 三氮杂十二烷二酸]2 - 用作肝胆磁共振造影剂的潜力。

材料与方法

使用1.5 - T扫描仪对正常大鼠和肝细胞癌(HCC)大鼠模型进行磁共振成像研究。研究组(N = 12)静脉注射0.1 mmol/kg[钆(苯甲酰基 - TTDA)]2 - ,对照组(N = 12)静脉注射0.1 mmol/kg钆喷酸葡胺(Gd - DTPA)2 - ,之后获取正常大鼠的连续多层T1加权快速场回波(TFE)(重复时间/回波时间/翻转角:15毫秒/6.1毫秒/25度)冠状位图像。研究组和对照组(每组N = 12)中植入HCC的大鼠采用类似的磁共振成像方案并额外采集T2加权图像。分析磁共振图像以评估正常肝脏、肾皮质、肾髓质和肿瘤的时间增强变化(信噪比[SI/N]增加百分比)。还评估了研究组和对照组中肝脏病变的对比噪声比(CNR)。最后一次磁共振扫描后立即处死大鼠进行尸检和组织病理学观察。同时也进行了小鼠急性毒性试验(半数致死剂量,LD50)。

结果

正常大鼠注射[钆(苯甲酰基 - TTDA)]2 - 后5 - 50分钟肝脏增强达到平台期,持续3小时,然后逐渐下降。注射[钆(苯甲酰基 - TTDA)]2 - 后肝脏、肾皮质和髓质的增强强度明显高于注射Gd - DTPA。在对比研究的早期动态阶段,注射[钆(苯甲酰基 - TTDA)]2 - 对肿瘤特征的显示效果与Gd - DTPA相似。然而,在后期肿瘤增强下降而肝脏增强持续时,研究组的肝脏病变CNR明显更高。[钆(苯甲酰基 - TTDA)]2 - 在小鼠急性毒性试验中的LD50剂量为7.5 mmol/kg。

结论

该动物研究的初步结果表明,[钆(苯甲酰基 - TTDA)]2 - 有潜力成为一种可靠的肝脏磁共振造影剂。

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