Israel Ina, Fluri Felix, Schadt Fabian, Buck Andreas K, Samnick Samuel
Department of Nuclear Medicine, University Hospital Wurzburg, 97080 Wurzburg, Germany.
Department of Neurology, University Hospital Wurzburg, 97080 Wurzburg, Germany.
Curr Neurovasc Res. 2018;15(1):55-62. doi: 10.2174/1567202615666180319152007.
P-selectin is activated early after stroke, followed by a rapid decline. This time course can be used to generate important information on stroke onset. The latter is crucial for therapeutic decision-making of wake-up strokes (i.e. thrombolysis or not). Here, we evaluated the specific p-selectin inhibitor fucoidan labeled with gallium-68 (68Ga-Fucoidan) as an imaging biomarker for assessing p-selectin activation in acute ischemic stroke using Positron Emission Tomography (PET).
68Ga-Fucoidan was investigated in rats brain at 2-5 h (n=16), and additionally at 24-26 h (n=9) and 48 h (n=3) after induction of photothrombic stroke or in sham-operated animals (n=6). Correlation of cerebral 68Ga-Fucoidan uptake with p-selectin expression was determined by exposing freshly cut brain cryosections to autoradiography and immunostaining using specific antibodies against p-selectin.
PET scans showed an increased accumulation of 68Ga-Fucoidan in the histologically proven ischemic stroke, as compared to the corresponding contralateral hemisphere in all except one animal. The median ratio between the uptake in the ischemic lesion and the contralateral region was 1.95 (1.45-2.41) at 2-5 h, 1.38 (1.05-1.89) at 24-26 h, and 1.09 (0.81-1.38) at 48 h after stroke, compared to 1.22 (0.99-1.49) for sham-operated animals. In the ex vivo autoradiography, 68Ga-Fucoidan accumulation co-localized with p-selectin as assessed by immunostaining. Control animals and those scanned at 24-26 h and 48 h after stroke exhibited no elevated 68Ga-Fucoidan uptake in either hemisphere.
PET imaging using 68Ga-Fucoidan represents a valuable tool for assessing p-selectin activation in vivo discriminating ischemic stroke early after stroke onset.
P-选择素在中风后早期被激活，随后迅速下降。这一动态过程可用于生成有关中风发作的重要信息。后者对于醒后中风（即是否进行溶栓治疗）的治疗决策至关重要。在此，我们评估了用镓-68（68Ga-岩藻依聚糖）标记的特异性P-选择素抑制剂岩藻依聚糖作为一种成像生物标志物，使用正电子发射断层扫描（PET）评估急性缺血性中风中P-选择素的激活情况。
在光血栓性中风诱导后2 - 5小时（n = 16）、24 - 26小时（n = 9）和48小时（n = 3）的大鼠脑中研究68Ga-岩藻依聚糖，另外在假手术动物（n = 6）中进行研究。通过将新鲜切割的脑冰冻切片进行放射自显影，并使用抗P-选择素的特异性抗体进行免疫染色，来确定脑内68Ga-岩藻依聚糖摄取与P-选择素表达之间的相关性。
PET扫描显示，在组织学证实的缺血性中风中，除一只动物外，所有动物的68Ga-岩藻依聚糖在缺血性中风中的蓄积均高于相应的对侧半球。中风后2 - 5小时，缺血性病变与对侧区域摄取的中位数比值为1.95（1.45 - 2.41），24 - 26小时为1.38（1.05 - 1.89），48小时为1.09（0.81 - 1.38），而假手术动物为1.22（0.99 - 1.49）。在体外放射自显影中，通过免疫染色评估，68Ga-岩藻依聚糖的蓄积与P-选择素共定位。对照动物以及在中风后24 - 26小时和48小时扫描的动物，其任一脑半球的68Ga-岩藻依聚糖摄取均未升高。
使用68Ga-岩藻依聚糖的PET成像代表了一种有价值的工具，可用于在体内评估中风发作后早期鉴别缺血性中风时的P-选择素激活情况。
