Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Mol Imaging Biol. 2012 Aug;14(4):500-8. doi: 10.1007/s11307-011-0512-4.
The goal of this study was to determine the specificity of ⁶⁴Cu-CB-TE2A-c(RGDyK) (⁶⁴Cu-RGD) for osteoclast-related diseases, such as Paget's disease or rheumatoid arthritis.
C57BL/6 mice were treated systemically with osteoprotegerin (OPG) for 15 days or RANKL for 11 days to suppress and stimulate osteoclastogenesis, respectively. The mice were then imaged by positron emission tomography/computed tomography using ⁶⁴Cu-RGD, followed by determination of serum TRAP5b and bone histology. Standard uptake values were determined to quantify ⁶⁴Cu-RGD in bones and other tissues.
Mice treated with OPG showed decreased bone uptake of ⁶⁴Cu-RGD at 1, 2, and 24 h post-injection of the tracer (p < 0.01 for all time points) compared to vehicle controls, which correlated with a post-treatment decrease in serum TRAP5b. In contrast, mice treated with RANKL showed significantly increased bone uptake at 2 h post-injection of (⁶⁴Cu-RGD (p < 0.05) compared to the vehicle control group, corresponding to increased serum TRAP5b and OC numbers as determined by bone histology.
These data demonstrate that ⁶⁴Cu-RGD localizes to areas in bone with increased osteoclast numbers and support the use of ⁶⁴Cu-RGD as an imaging biomarker for osteoclast number that could be used to monitor osteoclast-related pathologies and their treatments.
本研究旨在确定 ⁶⁴Cu-CB-TE2A-c(RGDyK)（⁶⁴Cu-RGD）对破骨细胞相关疾病（如 Pagets 病或类风湿关节炎）的特异性。
C57BL/6 小鼠通过全身给予护骨素（OPG）治疗 15 天或核因子κB 受体激活配体（RANKL）治疗 11 天，分别抑制和刺激破骨细胞生成。然后，使用 ⁶⁴Cu-RGD 通过正电子发射断层扫描/计算机断层扫描对小鼠进行成像，随后测定血清 TRAP5b 和骨组织学。标准摄取值用于定量骨骼和其他组织中的 ⁶⁴Cu-RGD。
与对照组相比，给予 OPG 治疗的小鼠在注射示踪剂后 1、2 和 24 小时时骨骼对 ⁶⁴Cu-RGD 的摄取减少（所有时间点均 p<0.01），这与治疗后血清 TRAP5b 下降有关。相比之下，给予 RANKL 治疗的小鼠在注射（⁶⁴Cu-RGD 后 2 小时时骨骼摄取显著增加（p<0.05），与骨组织学测定的血清 TRAP5b 和 OC 数量增加相对应。
这些数据表明， ⁶⁴Cu-RGD 定位于破骨细胞数量增加的骨骼区域，并支持将 ⁶⁴Cu-RGD 用作破骨细胞数量的成像生物标志物，可用于监测破骨细胞相关疾病及其治疗。
