Zhang Xin, Xin Jun, Shi Yu, Xu Weina, Yu Shupeng, Yang Zhiguang, Liu Changping, Cao Li, Guo Qiyong
Department of Radiology and Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Radiology and Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Nucl Med Biol. 2015 Mar;42(3):250-5. doi: 10.1016/j.nucmedbio.2014.11.007. Epub 2014 Nov 26.
Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose.
We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers.
The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94).
(99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs.
肝星状细胞（HSC）激活伴随着整合素αvβ3表达增加，是肝纤维化形成的一个重要因素。靶向整合素αvβ3的分子成像可为评估损伤肝脏中活化肝星状细胞（aHSCs）上整合素αvβ3的表达和功能提供一种非侵入性方法，进而提供重要的预后信息。（99m）Tc - 3PRGD2就是这样一种针对整合素αvβ3的放射性示踪剂。在本研究中，我们旨在比较正常肝脏和损伤肝脏对（99m）Tc - 3PRGD2的肝脏摄取和滞留差异，以评估（99m）Tc - 3PRGD2闪烁扫描用于此目的的可行性。
我们使用平面闪烁扫描评估静脉注射（99m）Tc - 3PRGD2后，硫代乙酰胺（TAA）诱导的肝纤维化大鼠肝脏中整合素αvβ3结合的变化，并与对照组进行比较。我们将冷的c（RGDyK）与（99m）Tc - 3PRGD2共同注射以评估放射性示踪剂的特异性结合。我们进行天狼星红染色以评估肝纤维化，进行免疫荧光共定位以确定纤维化肝脏中表达的整合素αvβ3的位置，并测量对照组和纤维化肝脏中整合素αvβ3和α - 平滑肌肌动蛋白（α - SMA）的蛋白质和信使RNA表达。
纤维化肝脏显示出（99m）Tc - 3PRGD2摄取和滞留增加。已证明放射性示踪剂与主要在aHSCs上表达的整合素αvβ3特异性结合。注射后30分钟时，纤维化肝脏的肝心比高于对照组肝脏（TAA组为1.98±0.08，对照组为1.50±0.12，p<0.01）。肝脏的t1/2比对照组更长（TAA组为27.07±10.69分钟，对照组为12.67±4.10分钟，p<0.01）。两组之间心脏t1/2的差异无统计学意义（TAA组为3.13±0.63分钟，对照组为3.41±0.77分钟，p = 0.94）。
（99m）Tc - 3PRGD2分子成像可为评估肝星状细胞激活提供一种非侵入性方法。
