钆（III）四氮杂卟啉配合物的临床前评估。一种用于磁共振成像的新型顺磁性造影剂。

Preclinical evaluation of gadolinium (III) texaphyrin complex. A new paramagnetic contrast agent for magnetic resonance imaging.

作者信息

Young S W, Sidhu M K, Qing F, Muller H H, Neuder M, Zanassi G, Mody T D, Hemmi G, Dow W, Mutch J D

机构信息

Department of Radiology, Stanford University School of Medicine.

出版信息

Invest Radiol. 1994 Mar;29(3):330-8. doi: 10.1097/00004424-199403000-00013.

DOI:10.1097/00004424-199403000-00013

PMID:8175308

Abstract

RATIONALE AND OBJECTIVES

Gadolinium III texaphyrin (Gd[III] texaphyrin) complex, a new magnetic resonance imaging contrast (MRI) agent, was evaluated.

METHODS

In vitro relaxivity (1.5 T) and stability studies (5% dextrose) were conducted. Subchronic toxicity (8 males, 8 females; 2-20 mumol Gd(III) texaphyrin complex/kg body weight; 3 times per week for 3 weeks). Biodistribution and excretion studies were conducted in Sprague-Dawley rats; MRI studies were conducted in normal and tumor-bearing rats and rabbits.

RESULTS

Relaxivity values were as follows: r1 = 19 (mumol/L.sec)-1 and r2 = 22 (mumol/L.sec)-1. The 21-day subchronic toxicity study revealed no abnormalities. The compound is stable. Biodistribution demonstrated liver uptake. Magnetic resonance imaging in normal (n = 34) and tumor-bearing (n = 4) rats and normal (n = 8) and tumor-bearing (n = 19) rabbits revealed: significant (P < .05) contrast enhancement of liver and kidney after 1-17 mumol/kg of Gd(III) texaphyrin complex. Gadolinium (III) texaphyrin complex (2.5 mumol/kg) produced significant contrast enhancement of liver carcinomas in rabbits (n = 8). Thigh V2 carcinomas (n = 22) had selective (P < .05) enhancement, 5 mumol/kg. In rat fibrosarcomas (n = 4), 17 mumol Gd(III) texaphyrin complex produced significant enhancement up to 24 hours.

CONCLUSIONS

Gadolinium (III) texaphyrin complex appears to be an effective and safe MRI contrast agent.

摘要

原理与目的

评估钆（III）替克卟啉（Gd[III]替克卟啉）复合物，一种新型磁共振成像造影剂。

方法

进行体外弛豫率（1.5 T）和稳定性研究（5%葡萄糖）。进行亚慢性毒性研究（8只雄性，8只雌性；2 - 20 μmol Gd(III)替克卟啉复合物/千克体重；每周3次，共3周）。在斯普拉格 - 道利大鼠中进行生物分布和排泄研究；在正常和荷瘤大鼠及兔中进行磁共振成像研究。

结果

弛豫率值如下：r1 = 19（μmol/L·秒）-1 且 r2 = 22（μmol/L·秒）-1。21天的亚慢性毒性研究未发现异常。该化合物稳定。生物分布显示肝脏摄取。在正常（n = 34）和荷瘤（n = 4）大鼠以及正常（n = 8）和荷瘤（n = 19）兔中的磁共振成像显示：给予1 - 17 μmol/kg的Gd(III)替克卟啉复合物后，肝脏和肾脏有显著（P <.05）的对比增强。钆（III）替克卟啉复合物（2.5 μmol/kg）使兔（n = 8）的肝癌有显著对比增强。大腿V2癌（n = 22）有选择性（P <.05）增强，剂量为5 μmol/kg。在大鼠纤维肉瘤（n = 4）中，17 μmol Gd(III)替克卟啉复合物在长达24小时内产生显著增强。