León E T, Rey A M, Savio E O, López J J, Kremer E, León A S
Cátedra de Radioquímica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):99-103.
The possibility of using 99mTc-labelled nucleotides as tumour seeking agents has been proposed by different research groups. We have recently reported the preparation of a 99mTc-ADP complex with a high radiochemical purity (> 95%), good in vitro and in vivo stability and promising biodistribution results when injected in mice bearing spontaneous mammary adenocarcinomas. Here we report the results of further investigations in animals with spontaneous neoplastic processes, including whole-body autoradiography in mice (20 minutes and 60 minutes post injection) and gamma-camera imaging studies in Wistar rats. Dynamic studies (up to 45 minutes) and static images (up to 18 hours) were acquired to determine the pharmacokinetics of 99mTc-ADP and the tumour/muscle and tumour/blood ratios. Blood-pool studies were also performed as a control. Tumours were visualized by autoradiography as was to be expected from the biodistribution studies. Dynamic studies showed a rapid blood clearance and a behaviour that fitted to a tricompartimental model. Radioactivity was rapidly taken up by the kidneys and excreted in the urine. No evidence of in vivo instability of the complex was observed. Tumour uptake reached the maximum values after 20 minutes post-injection. Tumour/blood and tumour/muscle ratios improved over time, enhancing tumour visualization. The best images were obtained after 3 hours post injection. In summary, our studies suggest that 99mTc-ADP is a promising radiopharmaceutical for tumour diagnosis.
不同研究小组已提出将99mTc标记的核苷酸用作肿瘤寻靶剂的可能性。我们最近报道了一种99mTc-ADP复合物的制备，其放射化学纯度高（>95%），体外和体内稳定性良好，在注射到患有自发性乳腺腺癌的小鼠体内时具有良好的生物分布结果。在此，我们报告在患有自发性肿瘤病变的动物中进行的进一步研究结果，包括对小鼠进行全身放射自显影（注射后20分钟和60分钟）以及对Wistar大鼠进行γ相机成像研究。采集动态研究（长达45分钟）和静态图像（长达18小时）以确定99mTc-ADP的药代动力学以及肿瘤/肌肉和肿瘤/血液比值。还进行了血池研究作为对照。正如生物分布研究所预期的那样，通过放射自显影可观察到肿瘤。动态研究显示血液清除迅速，其行为符合三室模型。放射性迅速被肾脏摄取并随尿液排出。未观察到该复合物在体内不稳定的迹象。注射后20分钟肿瘤摄取达到最大值。肿瘤/血液和肿瘤/肌肉比值随时间改善，增强了肿瘤的显影效果。注射后3小时获得最佳图像。总之，我们的研究表明99mTc-ADP是一种有前途的用于肿瘤诊断的放射性药物。
