Ge Pingju, Sheng Fugeng, Jin Yiguang, Tong Li, Du Lina, Zhang Lei, Tian Ning, Li Gongjie
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China.
Department of Radiology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
Biomed Pharmacother. 2016 Dec;84:423-429. doi: 10.1016/j.biopha.2016.09.061. Epub 2016 Sep 25.
Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd-diethylenetriaminepentaacetate-bis(alendronate) (Gd-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK, complex constant, and T relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r) of 7.613mMs (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd-DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd-DTPA-BA. The signal intensity of Gd-DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd-DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases.
磁共振成像（MR）目前用于骨肉瘤的诊断，但即便使用了造影剂，效果仍不尽人意。在此，我们报告一种新型的骨靶向MR成像造影剂，钆-二乙烯三胺五乙酸-双（阿仑膦酸盐）（Gd-DTPA-BA），用于骨肉瘤的诊断。它是一种趋骨细胞分子（即阿仑膦酸盐）与一种MR成像造影剂（即Gd-DTPA）的共轭物。我们测量了其理化参数，包括pK、络合常数和T弛豫率。通过测量其在羟基磷灰石上的吸附来评估其趋骨细胞能力。研究了其溶血情况。在健康裸鼠和荷骨肉瘤裸鼠上研究了Gd-DTPA-BA和Gd-DTPA的MR成像及生物分布。Gd-DTPA-BA在羟基磷灰石上显示出高吸附性、高MR弛豫率（r）为7.613 mM/s（是Gd-DTPA的2.6倍）且无溶血现象。静脉注射给小鼠后，Gd-DTPA-BA的MR造影效果远高于Gd-DTPA。更重要的是，Gd-DTPA-BA显著改善了骨肉瘤的MR成像。Gd-DTPA-BA在50分钟时的信号强度达到120.3%，相当于Gd-DTPA的三倍。荷骨肉瘤小鼠中Gd-DTPA-BA的骨靶向指数（骨/血）在180分钟时非常高，达到130。此外，由于骨肉瘤转移，在肺部也能发现造影剂增强。Gd-DTPA-BA在骨肉瘤的诊断中，包括原发性骨肿瘤和转移瘤，发挥着有前景的作用。
