评估99mTc(CO)5I作为一种潜在的肺灌注剂。
Evaluation of 99mTc(CO)5I as a potential lung perfusion agent.
作者信息
Miroslavov Alexander E, Gorshkov Nikolay I, Lumpov Alexander L, Yalfimov Anatoly N, Suglobov Dmitrii N, Ellis Beverley L, Braddock Rattana, Smith Anne-Marie, Prescott Mary C, Lawson Richard S, Sharma Harbans L
机构信息
Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia.
出版信息
Nucl Med Biol. 2009 Jan;36(1):73-9. doi: 10.1016/j.nucmedbio.2008.10.017.
INTRODUCTION
The use of (99m)Tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its potential as a lung perfusion agent.
METHODS
(99m)Tc(CO)(5)I was synthesized by carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using (99m)Tc-MAA.
RESULTS
Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood, 0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney, 0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney, 1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake.
CONCLUSION
(99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.
引言
（99m）锝-大颗粒白蛋白用于肺灌注显像在核医学中已得到充分确立。然而，由于存在感染因子污染的潜在风险，例如变异型克雅氏病，人们对使用血液制品存在安全担忧。初步研究表明，静脉注射后，Tc(CO)(5)I主要被肺部摄取。本研究的目的是评估（99m）Tc(CO)(5)I的生物分布和药代动力学及其作为肺灌注剂的潜力。
方法
在170℃、160个大气压的一氧化碳存在下，于碘化氢存在下，通过（99m）TcO(4-)的羰基化反应合成（99m）Tc(CO)(5)I，反应40分钟。使用（99）Tc(CO)(5)I作为参考，通过高效液相色谱法测定放射化学纯度。通过耳静脉注射将（99m）Tc(CO)(5)I给予三只南美栗鼠，使用伽马相机（西门子E-cam）在20分钟内采集动态图像。还使用（99m）锝标记的大颗粒白蛋白（（99m）Tc-MAA）和（99m）TcO(4-)进行成像研究以作比较。将（99m）Tc(CO)(5)I静脉注射给Sprague-Dawley大鼠，并在注射后15分钟和1小时进行组织分布研究。使用（99m）Tc-MAA进行比较研究。
结果
通过高效液相色谱法评估，放射化学纯度为98%。保留时间与（99）Tc(CO)(5)I相似。动态图像显示，70%的（99m）Tc(CO)(5)I迅速出现在肺部，并至少保持恒定20分钟。相比之下，（99m）TcO(4-)给药后迅速从肺部清除。正如预期的那样，（99m）Tc-MAA显示90%的肺部蓄积。（99m）Tc(CO)(5)I在1小时时每克器官注射剂量的百分比±标准差如下：血液，0.22±0.02；肺，12.8±2.87；肝脏，0.8±0.15；心脏，0.15±0.01；肾脏，0.47±0.08。1小时时每个器官注射剂量的百分比±标准差如下：肺，22.47±2.31；肝脏，10.53±1.8；心脏，0.18±0.01；肾脏，1.2±0.17。（99m）Tc-MAA的组织分布研究显示100%的肺部摄取。
结论
（99m）Tc(CO)(5)I以高放射化学纯度合成，并在肺部显示出高蓄积。有必要进一步研究（99m）锝-五羰基配合物肺部摄取的机制并进行优化。
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