当前位置: X-MOL 学术J Nucl. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Impact of Endothelial 18-kDa Translocator Protein on the Quantification of 18F-DPA-714
The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2018-02-01 , DOI: 10.2967/jnumed.117.195396
Catriona Wimberley , Sonia Lavisse , Vincent Brulon , Marie-Anne Peyronneau , Claire Leroy , Benedetta Bodini , Philippe Remy , Bruno Stankoff , Irène Buvat , Michel Bottlaender

18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.



中文翻译:

内皮18-kDa转运蛋白对18 F-DPA-714定量的影响

18 F-DPA-714是第二代示踪剂,用于18kDa转运蛋白(TSPO)(一种神经发炎的标志物)的PET成像。TSPO PET的分析和解释具有挑战性,尤其是因为TSPO的基础表达。这项研究的目的是评估一个隔室模型,该模型解释了内皮TSPO结合对来自健康受试者队列的18 F-DPA-714 PET扫描定量的影响。方法: 15名健康受试者(9种高亲和力结合剂和6种混合亲和力结合剂)进行了18次研究F-DPA-714 PET扫描具有动脉血取样和代谢物分析功能。使用2-组织隔室模型(2TC)以及带有额外的不可逆的用于内皮结合的隔室的2TC(2TC-1K)对动力学参数进行定量。这些区域参数和特定于内皮细胞的信使RNA(mRNA)表达与区域TSPO mRNA表达相关。结果: 2TC-1K模型比2TC更适合81%的拟合。与2TC相比,使用2TC-1K的所有区域的总发行量显着减少了21%±12%。内皮结合参数K b在整个脑区域中变化很大。ķ b与为TSPO mRNA表达提取的所有3种探针均具有强相关性(r = 0.80,r = 0.79和r = 0.90),但与2TC-1K的其他结合参数没有相关性。对于2TC,分布量和其中一种TSPO mRNA探针之间的相关性较低,但存在显着相关性(r = 0.65)。在TSPO的mRNA和内皮细胞特异的基因之间发现了很强的显着相关性。结论:在动力学模型中考虑内皮TSPO可改善PET数据的拟合度。K b之间的高度相关性TSPO mRNA提示2TC-1K模型比2TC揭示了更多关于TSPO区域密度的生物学信息。TSPO与内皮细胞mRNA之间的相关性支持K b的区域变化与内皮TSPO之间的关系。这些结果可以改善对18 F-DPA-714 PET结合参数估计的估计,尤其是在诱发血管变化的疾病中。

更新日期:2018-02-01
down
wechat
bug