Fernandes Renata S, Silva Juliana de Oliveira, Lopes Savia C A, Chondrogiannis Sotirios, Rubello Domenico, Cardoso Valbert N, Oliveira Mônica C, Ferreira Lucas A M, de Barros André L B
aDepartments of Clinical and Toxicological Analyses bPharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil cDepartment of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy.
Nucl Med Commun. 2016 Mar;37(3):307-12. doi: 10.1097/MNM.0000000000000443.
Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice.
Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection.
The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a β half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios.
DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.
恶性肿瘤的早期诊断对于成功制定根治性和治愈性治疗方案至关重要。在本研究中，我们描述了在生理pH值下对阿霉素（DOX）进行直接放射性标记，以识别携带小鼠乳腺肿瘤（4T1细胞）的BALB/c小鼠。
通过在氯化亚锡存在下，将高锝酸盐-99m（99mTc）加入含有DOX的磷酸盐缓冲盐水（PBS，pH 7.4）溶液中来制备99mTc-DOX。测定放射化学纯度和体外稳定性。通过测量健康动物的血液放射性来确定99mTc-DOX的循环时间。在注射后1、4和8小时，对荷瘤小鼠进行闪烁成像和生物分布研究。
99mTc-DOX复合物显示出高放射化学纯度（99.27±0.34%），并且在8小时内具有体外稳定性。血液中的Tc-DOX水平呈双相下降，α半衰期为4.5分钟，β半衰期为277.2分钟。由于药物的消除途径，肾脏、肝脏和脾脏摄取较高。此外，肿瘤摄取高于对照组织，导致肿瘤与肌肉的比例较高。
DOX成功地用高锝酸盐-99m标记，并显示出高稳定性。生物分布和闪烁成像研究表明，在携带乳腺肿瘤的BALB/c小鼠中，肿瘤与肌肉的比例较高。这些结果表明99mTc-DOX作为肿瘤诊断功能剂的可行性。
