Lan J A, Chervu L R, Johansen K L, Wolkoff A W
Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York.
Gastroenterology. 1988 Dec;95(6):1625-31. doi: 10.1016/s0016-5085(88)80087-8.
Quantitation of initial uptake of the cholescintigraphy agents, 99mTc-Lidofenin, 99mTc-Disofenin, 99mTc-Mebrofenin, and 99mTc-Arclofenin, in short-term cultured rat hepatocytes revealed a marked reduction at 4 degrees C as compared with 37 degrees C. Depletion of adenosine triphosphate by preincubation of cells in sodium azide and 2-deoxyglucose reduced initial uptake of 99mTc-Disofenin at 37 degrees C by 50% (p less than 0.05), suggesting an energy-dependent mechanism. At 37 degrees C, 99mTc-Mebrofenin and 99mTc-Disofenin had the greatest rate of uptake. 99mTc-Disofenin and 99mTc-Lidofenin uptake was inhibited by 20 microM sulfobromophthalein, bilirubin, taurocholate, deoxycholate, chenodeoxycholate, and cholate, suggesting a common anionic transport mechanism. Uptake of 99mTc-Disofenin was unaffected by removal of NaCl from medium, suggesting that its transport did not proceed by the primary high-affinity uptake pathways associated with sulfobromophthalein and taurocholate, which require Cl- and Na+, respectively. 99mTc-Mebrofenin uptake was inhibited only modestly by taurocholate, deoxycholate, and bilirubin (p less than 0.05) and 99mTc-Arclofenin uptake was not inhibited by the organic anions studied. These results suggest that 99mTc-Mebrofenin and 99mTc-Arclofenin might be advantageous for cholescintigraphy in severely jaundiced patients. The relatively simple in vitro methodology described in this study may be useful in the design and screening of potential new agents before proceeding to animal studies or clinical trials.
对短期培养的大鼠肝细胞中99m锝-利多氟宁、99m锝-地索氟宁、99m锝-美布芬宁和99m锝-阿氯芬宁等肝胆闪烁造影剂初始摄取量的定量分析显示，与37℃相比，4℃时摄取量显著降低。通过在叠氮化钠和2-脱氧葡萄糖中预孵育细胞来耗尽三磷酸腺苷，使37℃时99m锝-地索氟宁的初始摄取量降低了50%（p<0.05），提示存在能量依赖机制。在37℃时，99m锝-美布芬宁和99m锝-地索氟宁的摄取速率最高。99m锝-地索氟宁和99m锝-利多氟宁的摄取受到20微摩尔磺溴酞、胆红素、牛磺胆酸盐、脱氧胆酸盐、鹅去氧胆酸盐和胆酸盐的抑制，提示存在共同的阴离子转运机制。从培养基中去除氯化钠对99m锝-地索氟宁的摄取没有影响，表明其转运不是通过与磺溴酞和牛磺胆酸盐相关的主要高亲和力摄取途径进行的，后者分别需要氯离子和钠离子。牛磺胆酸盐、脱氧胆酸盐和胆红素对99m锝-美布芬宁摄取的抑制作用较小（p<0.05），而所研究的有机阴离子对99m锝-阿氯芬宁的摄取没有抑制作用。这些结果表明，99m锝-美布芬宁和99m锝-阿氯芬宁可能对严重黄疸患者的肝胆闪烁造影有利。本研究中描述的相对简单的体外方法可能有助于在进行动物研究或临床试验之前设计和筛选潜在的新药物。
