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

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 pK_a, 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^-1s^-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.