1.Synthesis, preclinical evaluation and pilot clinical study of a P2Y12 receptor targeting radiotracer 18FQTFT for imaging brain disorders by visualizing anti-inflammatory microglia.
Bolin YAO ; Yanyan KONG ; Jianing LI ; Fulin XU ; Yan DENG ; Yuncan CHEN ; Yixiu CHEN ; Jian CHEN ; Minhua XU ; Xiao ZHU ; Liang CHEN ; Fang XIE ; Xin ZHANG ; Cong WANG ; Cong LI
Acta Pharmaceutica Sinica B 2025;15(2):1056-1069
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled PET tracer (QTFT) that targets the P2Y12, a receptor highly expressed on anti-inflammatory microglia. [18F]QTFT exhibited high binding affinity to the P2Y12 (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [18F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y12 antagonist. Furthermore, [18F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y12 in anti-inflammatory microglia. In a pilot clinical study, [18F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [18F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y12 overexpressed in anti-inflammatory microglia.
2.The relationship between internal carotid artery wall shear stress and carotid plaque neovascularization was evaluated by carotid color ultrasound
Yuncan WANG ; Guangyun CAO ; Haibo WU ; Na WANG
The Journal of Practical Medicine 2024;40(22):3232-3237
Objective To assess the correlation between wall shear stress(WSS)in the internal carotid artery and neovascularization of carotid plaque using color ultrasound imaging.Methods A total of 99 patients diag-nosed with carotid atherosclerotic plaque(CAP)were prospectively selected between July 2021 and September 2023.All patients underwent comprehensive carotid imaging including color ultrasound,conventional ultrasound,and carotid contrast-enhanced ultrasound(CEUS).Based on the presence or absence of intraplaque neovasculariza-tion(IPN)in patients with ischemic cerebrovascular disease,they were categorized into the forming group and non-forming group.Comparative analysis was performed on wall shear stress(WSS)values and clinical data between these two groups to identify factors influencing IPN formation in the carotid artery among patients with ischemic cere-brovascular disease,while also assessing the predictive value of average WSS for IPN formation.Results Among 99 patients with ischemic cerebrovascular disease,carotid artery IPN was observed in 23 cases,while the remaining 76 cases did not exhibit carotid artery IPN.The formation group demonstrated significantly higher levels of white blood cell count,plaque thickness,plaque length,stenosis≥70%ratio,C-reactive protein,and matrix metallopro-teinase-9 to tissue inhibitor of matrix metalloproteinase-1(MMP-9/TIMP-1)ratio compared to the non-formation group(P<0.05).Logistic regression analysis revealed that mean wall shear stress(OR=4.545;95%CI:1.998~10.339),stenosis severity(OR=2.765;95%CI:1.215~6.290),C-reactive protein levels(OR=3.047;95%CI:1.339~6.930),and MMP-9/TIMP-1 ratio(OR=3.543;95%CI:1.558~8.060)were significant influencing factors for carotid artery IPN formation in patients with ischemic cerebrovascular disease(P<0.05).The receiver operating characteristic curve(ROC)analysis revealed that the area under the curve(AUC)for average WSS in predicting carotid artery intraplaque neovascularization formation in patients with ischemic cerebrovascular disease was 0.797(P<0.05).At an average WSS of 10.23 dyne/cm2,the maximum specificity and sensitivity were deter-mined to be 85.53%and 78.26%,respectively.Conclusion The mean WSS of internal carotid artery has a good value in predicting the formation of carotid IPN in patients with ischemic cerebrovascular disease.

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