ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, New Illawarra Rd, Lucas Heights, Sydney, NSW 2234, Australia.
Eur J Nucl Med Mol Imaging. 2011 Aug;38(8):1516-28. doi: 10.1007/s00259-011-1784-2. Epub 2011 Apr 12.
The purpose of this study was to assess the feasibility and sensitivity of the high-affinity translocator protein (TSPO) ligand [(123)I]-CLINDE in imaging TSPO changes in vivo and characterise and compare astroglial and TSPO changes in the cuprizone model of demyelination and remyelination in C57BL/6 mice.
C57BL/6 mice were fed with cuprizone for 4 weeks to induce demyelination followed by 2-4 weeks of standard diet (remyelination). Groups of mice were followed by in vivo single photon emission computed tomography (SPECT)/CT imaging using [(123)I]-CLINDE and uptake correlated with biodistribution, autoradiography, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR).
The uptake of [(123)I]-CLINDE in the brain as measured by SPECT imaging over the course of treatment reflects the extent of the physiological response, with significant increases observed during demyelination followed by a decrease in uptake during remyelination. This was confirmed by autoradiography and biodistribution studies. A positive correlation between TSPO expression and astrogliosis was found and both activated astrocytes and microglial cells expressed TSPO. [(123)I]-CLINDE uptake reflects astrogliosis in brain structures such as corpus callosum, caudate putamen, medium septum and olfactory tubercle as confirmed by both in vitro and in vivo results.
The dynamics in the cuprizone-induced astroglial and TSPO changes, observed by SPECT imaging, were confirmed by immunofluorescence, RT-PCR and autoradiography. The highly specific TSPO radioiodinated ligand CLINDE can be used as an in vivo marker for early detection and monitoring of a variety of neuropathological conditions using noninvasive brain imaging techniques.
本研究旨在评估高亲和力转位蛋白（TSPO）配体[123I]-CLINDE 在体内成像 TSPO 变化的可行性和敏感性，并对脱髓鞘和再髓鞘的杯状朊病毒模型中的星形胶质细胞和 TSPO 变化进行特征描述和比较。
C57BL/6 小鼠用杯状朊病毒喂养 4 周以诱导脱髓鞘，然后用标准饮食喂养 2-4 周（再髓鞘）。通过使用[123I]-CLINDE 的体内单光子发射计算机断层扫描（SPECT）/CT 成像和生物分布、放射自显影、免疫组织化学、免疫荧光和实时聚合酶链反应（RT-PCR）来追踪各组小鼠。
SPECT 成像测量的治疗过程中大脑中[123I]-CLINDE 的摄取反映了生理反应的程度，在脱髓鞘期间观察到明显增加，然后在再髓鞘期间摄取减少。这一点得到了放射自显影和生物分布研究的证实。发现 TSPO 表达与星形胶质细胞增生之间存在正相关，激活的星形胶质细胞和小胶质细胞均表达 TSPO。[123I]-CLINDE 摄取反映了胼胝体、尾状核、中隔和嗅结节等脑结构中的星形胶质细胞增生，这一点通过体外和体内结果得到了证实。
SPECT 成像观察到的杯状朊病毒诱导的星形胶质细胞和 TSPO 变化的动力学，通过免疫荧光、RT-PCR 和放射自显影得到了证实。高特异性 TSPO 放射性碘标记配体 CLINDE 可作为一种体内标志物，用于使用非侵入性脑成像技术早期检测和监测各种神经病理学状况。
