使用[(18)F]DPA - 714正电子发射断层扫描（PET）对脑内注射脂多糖诱导的局部神经炎症大鼠模型中TSPO过表达进行定量分析。
Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [(18)F]DPA-714 PET.
作者信息
Ory Dieter, Postnov Andrey, Koole Michel, Celen Sofie, de Laat Bart, Verbruggen Alfons, Van Laere Koen, Bormans Guy, Casteels Cindy
机构信息
Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000, Leuven, Belgium.
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
出版信息
Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):163-172. doi: 10.1007/s00259-015-3172-9. Epub 2015 Sep 1.
PURPOSE
[(18)F]DPA-714 is a radiotracer with high affinity for TSPO. We have characterized the kinetics of [(18)F]DPA-714 in rat brain and evaluated its ability to quantify TSPO expression with PET using a neuroinflammation model induced by unilateral intracerebral injection of lipopolysaccharide (LPS).
METHODS
Dynamic small-animal PET scans with [(18)F]DPA-714 were performed in Wistar rats on a FOCUS-220 system for up to 3 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Full kinetic modelling of [(18)F]DPA-714 brain uptake was performed using a metabolite-corrected arterial plasma input function. Binding potential (BPND) calculated as the distribution volume ratio minus one (DVR-1) between affected and healthy brain tissue was used as the outcome measure and evaluated against reference tissue models.
RESULTS
The percentage of intact [(18)F]DPA-714 in arterial plasma samples was 92 ± 4 % at 10 min, 75 ± 8 % at 40 min and 52 ± 6 % at 180 min. The radiometabolite fraction in brain was negligible (<3 % at 30 min). Among the models investigated, the reversible two-tissue (2T) compartment model best described [(18)F]DPA-714 brain kinetics. BPND values obtained with a simplified and a multilinear reference tissue model (SRTM, MRTM) using the contralateral striatum as the reference region correlated well (Spearman's r = 0.96, p ≤ 0.003) with 2T BPND values calculated as DVR-1, and showed comparable bias (bias range 17.94 %, 20.32 %). Analysis of stability over time suggested that the acquisition time should be at least 90 min for SRTM and MRTM.
CONCLUSION
Quantification of [(18)F]DPA-714 binding to TSPO with full kinetic modelling is feasible using a 2T model. SRTM and MRTM can be suggested as reasonable substitutes with the contralateral striatum as the reference region and a scan duration of at least 90 min. However, selection of the reference region depends on the disease model used.
目的
[18F]DPA - 714是一种对转运蛋白18kDa（TSPO）具有高亲和力的放射性示踪剂。我们已对[18F]DPA - 714在大鼠脑中的动力学特征进行了表征，并使用单侧脑内注射脂多糖（LPS）诱导的神经炎症模型，评估了其通过正电子发射断层扫描（PET）定量TSPO表达的能力。
方法
在FOCUS - 220系统上对Wistar大鼠进行长达3小时的[18F]DPA - 714动态小动物PET扫描。使用高效液相色谱法（HPLC）分析血浆和灌注脑匀浆，以定量放射性代谢物。使用代谢物校正的动脉血浆输入函数对[18F]DPA - 714脑摄取进行完整的动力学建模。将受影响和健康脑组织之间的分布体积比减一（DVR - 1）计算得出的结合潜能（BPND）用作结果指标，并根据参考组织模型进行评估。
结果
动脉血浆样本中完整的[18F]DPA - 714百分比在10分钟时为92±4%，40分钟时为75±8%，180分钟时为52±6%。脑中的放射性代谢物分数可忽略不计（30分钟时<3%）。在所研究的模型中，可逆双组织（2T）隔室模型最能描述[18F]DPA - 714的脑动力学。使用对侧纹状体作为参考区域，通过简化和多线性参考组织模型（SRTM，MRTM）获得的BPND值与以DVR - 1计算的2T BPND值相关性良好（斯皮尔曼相关系数r = 0.96，p≤0.003），并且显示出相当的偏差（偏差范围为17.94%，20.32%）。随时间稳定性分析表明，SRTM和MRTM的采集时间应至少为90分钟。
结论
使用2T模型通过完整动力学建模定量[18F]DPA - 714与TSPO的结合是可行的。可以建议将SRTM和MRTM作为合理的替代方法，以对侧纹状体作为参考区域，扫描持续时间至少为90分钟。然而，参考区域的选择取决于所使用的疾病模型。
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