Ergün E L, Ercan M T, Selek H, Kaş H S, Ruacan S, Unsal I S, Mutlu M
Hacettepe University, Department of Nuclear Medicine, Ankara, Turkey.
J Microencapsul. 2000 Jul-Aug;17(4):509-18. doi: 10.1080/026520400405750.
Radioembolization is used in diagnostic imaging of the lungs and for radioembolization therapy of hepatic tumours. Presently, 99mTc labelled macroaggregates or microspheres of human serum albumin (HAM) are used for this purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is not a blood product. The aim of the present study was to evaluate the uptake and biodegradation of PLA microspheres in lungs. PLA (MW = 48720 Da) microspheres of 1.0-100 microm (mean = 39.5 microm) in diameter were prepared by solvent evaporation from methylene chloride. They were labelled with 99mTc by stannous chloride reduction at pH 3, with an efficiency of 98% and a stability of 96% at 24 h. For biodistribution studies, 15 mice were i.v. injected with 20 microCi 99mTc-PLA microspheres in 0.1 ml and sacrificed at 15 min, 1, 3, 6 and 24 h (three at each time point). All the organs were removed, weighed and counted against a standard prepared from 1/100 dilution of the injected radioactivity. Some mice were similarly injected and sacrificed at 30 min, 15 and 30 days. The lungs were removed and frozen, and 10 microm sections were obtained, stained with haemotoxylin and eosin and examined under a light microscope. Five rabbits were i.v. injected with 1 mCi of 99mTc-PLA microspheres. Scintigrams were obtained at various intervals up to 24 h. In mice, the lung uptake was significant at 30 min-1h post-injection. In rabbits, the lungs were the only organs visualized up to 24 h. Microscopic examination of tissue sections demonstrated slow biodegradation of PLA particles. In conclusion; (1) The high lung uptake obtained in mice and rabbits indicates the suitability of PLA microspheres for lung imaging, and (2) although the slow biodegradation rate might be a disadvantage in patients with lung disorders in diagnostic studies, it may be an advantage in therapeutic applications with radionuclides which have long physical half lives.
放射性栓塞术用于肺部的诊断成像以及肝肿瘤的放射性栓塞治疗。目前，99mTc标记的人血清白蛋白（HAM）大聚合体或微球用于此目的。聚乳酸（PLA）与HAM一样可生物降解，且与HAM不同的是，它不是血液制品。本研究的目的是评估PLA微球在肺部的摄取和生物降解情况。通过从二氯甲烷中蒸发溶剂制备直径为1.0 - 100微米（平均 = 39.5微米）的PLA（分子量 = 48720道尔顿）微球。它们在pH 3条件下通过氯化亚锡还原法用99mTc标记，标记效率为98%，24小时时稳定性为96%。对于生物分布研究，15只小鼠经静脉注射0.1毫升含20微居里99mTc - PLA微球的溶液，并在15分钟、1小时、3小时、6小时和24小时处死（每个时间点3只）。取出所有器官，称重并与由注射放射性活度的1/100稀释液制备的标准品进行计数比较。一些小鼠以类似方式注射并在30分钟、15天和30天处死。取出肺脏并冷冻，制备10微米切片，用苏木精和伊红染色并在光学显微镜下检查。5只兔子经静脉注射1毫居里的99mTc - PLA微球。在长达24小时的不同时间间隔获取闪烁扫描图。在小鼠中，注射后30分钟至1小时肺摄取显著。在兔子中，直至24小时肺部是唯一显影的器官。组织切片的显微镜检查显示PLA颗粒生物降解缓慢。总之；（1）在小鼠和兔子中获得的高肺摄取表明PLA微球适用于肺部成像，并且（2）尽管缓慢的生物降解速率在肺部疾病患者的诊断研究中可能是一个缺点，但在使用物理半衰期长的放射性核素的治疗应用中可能是一个优点。
