León A S, Rey A M, Leon E T, Savio E O, Kremer C, Lacava C J, Nappa A N, Chiozzone R N, Campos E D
Catedra de Radioquimica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
Q J Nucl Med. 1996 Jun;40(2):170-5.
A study of 99mTc-adenosine-5'-diphosphate (99mTc-ADP) as a radiopharmaceutical for tumour diagnosis is presented. Two different labelling methods, using SnCl2 in alkaline solution and Zn as reducing agents, were developed. Reduction with Sn(II) alkaline solution was the selected method because a lower concentration of ADP (0.5 mg/mL) could be used and a higher radiochemical yield was achieved. A labelled molecule with a radiochemical purity higher than 95%, in vitro stability of at least 6 hours and an over all negative charge was obtained Biodistribution studies carried out in normal mice and rats revealed rapid urinary excretion and no specific accumulation of activity in any other particular organ. This behaviour was similar to that reported for 99mTc-adenosine-5'-triphosphate (99mTc-ATP). Rapid blood clearance, that could be fitted to a bicompartimental model, was also verified. No evidence of in vivo instability was observed. Studies in mice and rats bearing spontaneous mammary adenocarcinomas were performed and the results were compared to those from the 99mTc-ATP studies. Although the tumour models used were not the same, the incorporation of both labelled compounds was very similar. Radioactivity uptake in the tumour and the tumour-to-blood ratio were not notably high. However, a significant increment was observed in the tumour-to-muscle ratio (1.0 +/- 0.2 at 30 minutes to 2.7 +/- 0.4 at 240 minutes). Whole-body autoradiography enabled tumour visualization. Further investigations, including scintigraphic imaging, must be carried to complete the clinical evaluation of 99mTc-ADP as a tumour seeking agent.
本文介绍了一项关于99mTc-腺苷-5'-二磷酸(99mTc-ADP)作为肿瘤诊断放射性药物的研究。开发了两种不同的标记方法,分别使用碱性溶液中的SnCl2和Zn作为还原剂。选择用Sn(II)碱性溶液进行还原,因为可以使用较低浓度的ADP(0.5mg/mL),并获得了更高的放射化学产率。得到了一种放射化学纯度高于95%、体外稳定性至少为6小时且整体带负电荷的标记分子。在正常小鼠和大鼠中进行的生物分布研究表明,其尿排泄迅速,且在任何其他特定器官中均无活性的特异性蓄积。这种行为与报道的99mTc-腺苷-5'-三磷酸(99mTc-ATP)相似。还证实了其血液清除迅速,符合双室模型。未观察到体内不稳定的证据。对患有自发性乳腺腺癌的小鼠和大鼠进行了研究,并将结果与99mTc-ATP研究的结果进行了比较。尽管使用的肿瘤模型不同,但两种标记化合物的摄取非常相似。肿瘤中的放射性摄取和肿瘤与血液的比值并不特别高。然而,观察到肿瘤与肌肉的比值有显著增加(30分钟时为1.0±0.2,240分钟时为2.7±0.4)。全身放射自显影能够显示肿瘤。必须进行包括闪烁成像在内的进一步研究,以完成对99mTc-ADP作为肿瘤靶向剂的临床评估。