Liu Shuang, He Zhengjie, Hsieh Wen-Yuan, Kim Young-Seung
School of Health Sciences, Purdue University, Lafayette, IN 47907, USA.
Nucl Med Biol. 2006 Apr;33(3):419-32. doi: 10.1016/j.nucmedbio.2006.01.005.
This report describes the evaluation of a series of novel cationic (99m)Tc-nitrido complexes, [(99m)TcN(DTC)(PNP)]+ (DTC = crown ether-containing dithiocarbamates; PNP = bisphosphine), as potential radiotracers for myocardial perfusion imaging. Synthesis of cationic (99m)Tc-nitrido complexes was accomplished in two steps according to literature methods. Biodistribution studies were performed in rats. Planar images of Sprague-Dawley rats administered with 15+/-2 MBq of cationic (99m)Tc radiotracer were obtained using a PhoGama large field-of-view Anger camera. Samples from both urine and feces were analyzed by a reversed-phase radio-HPLC method. Results from biodistribution studies showed that most of the cationic (99m)Tc-nitrido complexes have a high initial heart uptake with a long myocardial retention. They also show a rapid clearance from the liver and lungs. Cationic complexes [(99m)TcN(L2)(L6)]+ and [(99m)TcN(L4)(L6)]+ show heart/liver ratios four to five times better than that of (99m)Tc-sestamibi due to their much faster liver clearance. Their heart uptake and heart/liver ratio are comparable to that of (99m)TcN-DBODC5 within the experimental error. These findings have been confirmed by the results from imaging studies. Radio-HPLC analysis of urine and feces samples indicated that there was very little metabolism of cationic (99m)Tc-nitrido complexes in rats under anesthesia. The key finding of this study is that lipophilicity remains the most important factor affecting both heart uptake and target-to-background (T/B) ratios. Crown ethers are very useful functional groups to improve the liver clearance of cationic (99m)Tc-nitrido complexes. It is the combination of the appropriate DTCs and bisphosphines that results in cationic (99m)Tc-nitrido complexes with high heart uptake and fast clearance from the liver at the same time. The fast liver clearance of [(99m)TcN(L2)(L6)]+ and [(99m)TcN(L4)(L6)]+ suggests that they might be used to obtain clinically useful images as early as 30 min postinjection. [(99m)TcN(L2)(L6)]+ and [(99m)TcN(L4)(L6)]+ are very promising candidates for further evaluation in more extensive preclinical animal models.
本报告描述了一系列新型阳离子（99m）Tc-氮化物配合物[（99m）TcN（DTC）（PNP）]+（DTC =含冠醚的二硫代氨基甲酸盐；PNP =双膦）作为心肌灌注显像潜在放射性示踪剂的评估。阳离子（99m）Tc-氮化物配合物的合成按照文献方法分两步完成。在大鼠身上进行了生物分布研究。使用PhoGama大视野安格相机获取给予15±2 MBq阳离子（99m）Tc放射性示踪剂的Sprague-Dawley大鼠的平面图像。通过反相放射性高效液相色谱法分析尿液和粪便样本。生物分布研究结果表明，大多数阳离子（99m）Tc-氮化物配合物初始心脏摄取高且心肌滞留时间长。它们还显示出从肝脏和肺部的快速清除。阳离子配合物[（99m）TcN（L2）（L6）]+和[（99m）TcN（L4）（L6）]+的心脏/肝脏比值比（99m）Tc- sestamibi高四到五倍，因为它们的肝脏清除速度快得多。在实验误差范围内，它们的心脏摄取和心脏/肝脏比值与（99m）TcN-DBODC5相当。这些发现已通过成像研究结果得到证实。尿液和粪便样本的放射性高效液相色谱分析表明，麻醉大鼠体内阳离子（99m）Tc-氮化物配合物的代谢非常少。本研究的关键发现是亲脂性仍然是影响心脏摄取和靶本底（T/B）比值的最重要因素。冠醚是改善阳离子（99m）Tc-氮化物配合物肝脏清除的非常有用的官能团。正是合适的二硫代氨基甲酸盐和双膦的组合导致了同时具有高心脏摄取和快速肝脏清除的阳离子（99m）Tc-氮化物配合物。[（99m）TcN（L2）（L6）]+和[（99m）TcN（L4）（L6）]+的快速肝脏清除表明它们可能早在注射后30分钟就可用于获得临床有用的图像。[（99m）TcN（L2）（L6）]+和[（99m）TcN（L4）（L6）]+是在更广泛的临床前动物模型中进行进一步评估的非常有前景的候选物。
