Chervu L R, Joseph J A, Chun S B, Rolleston R E, Synnes E I, Thompson L M, Aldis A E, Rosenthall L
Albert Einstein College of Medicine, Department of Nuclear Medicine, Bronx, NY.
Eur J Nucl Med. 1988;14(9-10):441-5. doi: 10.1007/BF00252386.
IDA derivatives of three substituted benzothiazol, and two substituted chlorophenyl and one substituted pyrazoline compounds have been labeled with 99mTc and screened with four rat models with hepatocellular dysfunction manifesting varying degrees of change of liver architecture and hepatocellular damage associated with an active parenchymal destruction, fatty metamorphosis and cirrhosis. Organ distribution studies at 1 h postinjection have been compared in normal and diseased animal models for each agent labeled with 99mTc and with 99mTc-Disofenin (Disida) and Lidofenin (Hida) and 131I-Rose Bengal. From the data obtained with the six new IDA derivatives, the distribution kinetics of 99mTc-Arclophenin, (N-N'-2-benzoyl-4-chlorophenyl)carbamoylmethyl) imino diacetic acid (Phenida), are closely comparable to 99mTc-Disofenin in all animal models. Crossover patient studies (n = 14) for clinical evaluation of 99mTc-Arclophenin vs 99mTc-Disofenin indicate the close similarity of the 2 agents with regard to blood pool retention, gross liver/heart ratios and liver washout, suggesting Arclofenin as a suitable agent for hepatobiliary function studies. The impaired hepatocellular animal models presented should serve for fast screening of hepatobiliary agents and enable comparison of a series of closely related compounds.
三种取代苯并噻唑、两种取代氯苯和一种取代吡唑啉化合物的IDA衍生物已用99mTc标记，并在四种肝细胞功能障碍大鼠模型中进行筛选，这些模型表现出不同程度的肝结构变化和与实质性破坏、脂肪变性和肝硬化相关的肝细胞损伤。在注射后1小时对用99mTc标记的每种试剂以及99mTc-二异丙酚（Disida）、利多酚宁（Hida）和131I-玫瑰红在正常和患病动物模型中的器官分布研究进行了比较。从六种新的IDA衍生物获得的数据来看，99mTc-阿氯芬宁（N-N'-2-苯甲酰基-4-氯苯基）氨基甲酰甲基）亚氨基二乙酸（Phenida）在所有动物模型中的分布动力学与99mTc-二异丙酚密切可比。对99mTc-阿氯芬宁与99mTc-二异丙酚进行临床评估的交叉患者研究（n = 14）表明，这两种试剂在血池滞留、肝脏/心脏总比值和肝脏洗脱方面非常相似，表明阿氯芬宁是一种适合用于肝胆功能研究的试剂。所呈现的肝细胞受损动物模型应有助于快速筛选肝胆试剂，并能够比较一系列密切相关的化合物。
