Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent

Pingju Ge, Fugeng Sheng, Yiguang Jin, Li Tong, Lina Du, Lei Zhang, Ning Tian, Gongjie Li
Biomedicine & Pharmacotherapy 2016, 84: 423-429
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, Gd2-diethylenetriaminepentaacetate-bis(alendronate) (Gd2-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 pKa, complex constant, and T1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd2-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd2-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r1) of 7.613mM(-1)s(-1) (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd2-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 Gd2-DTPA-BA. The signal intensity of Gd2-DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd2-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. Gd2-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases.

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