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 pKa, complex constant, and T1relaxivity. 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.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China.
Pingju
P
Ge
Department of Radiology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
Fugeng
F
Sheng
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China. Electronic address: jinyg@bmi.ac.cn.
Yiguang
Y
Jin
College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Li
L
Tong
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Lina
L
Du
Department of Radiology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
Lei
L
Zhang
Department of Radiology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
Ning
N
Tian
Department of Radiology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China. Electronic address: ligj307@163.com.
Gongjie
G
Li
D019386:Alendronate / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012516:Osteosarcoma / Q000175:diagnosis*; D012815:Signal Processing, Computer-Assisted; D014018:Tissue Distribution / Q000187:drug effects
D001672:Biocompatible Materials; D003287:Contrast Media; D017886:Durapatite; D019786:Gadolinium DTPA; D019386:Alendronate
Alendronate; Bone targeting; Contrast agent; Gd-DTPA; Magnetic resonance imaging; Osteosarcoma