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 K_b varied highly across brain regions. K_b 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 K_b 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 K_b 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.

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。