Accelerated blood clearance of targeted ultrasound contrast reduced molecular imaging signal intensity: Secreted Frizzled Related Protein-2 signal remained significantly higher than signal from either Vascular Endothelial Growth Factor Receptor-2 or alpha
Accelerated blood clearance of targeted ultrasound contrast reduced molecular imaging signal intensity: Secreted Frizzled Related Protein-2 signal remained significantly higher than signal from either Vascular Endothelial Growth Factor Receptor-2 or alpha
复制标题
目标超声造影剂的加速血液清除降低了分子成像信号强度：分泌的卷曲相关蛋白 2 信号仍然显着高于血管内皮生长因子受体 2 或 α 的信号
DOI：
10.1109/ultsym.2019.8925919
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Dayton,PaulA
中科院分区：
文献类型：
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作者：
Tsuruta,James;White,Rachel;Klauber-DeMore,Nancy;Dayton,PaulA
多剂量的聚乙二醇（PEG）修饰药物由于产生对PEG片段反应的抗体而导致加速血液清除（ABC）。由于微泡脂质壳中PEG链的ABC效应，使用分子成像来监测治疗反应可能会变得复杂。我们的目的是在纵向成像研究中测量流过非肿瘤组织的靶向造影剂的半衰期，并确定哪种靶向造影剂在肿瘤内返回最高的信号强度。造影剂靶向三个不同的分子靶标，分泌卷曲相关蛋白2 (SFRP2)，血管内皮生长因子受体2 (VEGFR2)， AlphaVBeta3整合素（avb3）的分子成像信号均与造影剂半衰期显著相关。在限制半衰期相似的影像学检查之前和之后，SFRP2的分子成像信号仍然明显高于针对VEGFR2或avb3的超声造影返回的信号。我们假设，在我们的纵向研究中，免疫清除率的增加限制了能够灌注肿瘤血管的靶向造影剂的数量，这导致了分子成像信号的整体剂量依赖性下降。随着纵向研究的进展和造影剂半衰期的减少，分子成像可能会低估生物标志物水平，除非造影剂剂量是通过能够到达肿瘤和周围组织的造影剂量而不是注射剂量来标准化的。
Multiple doses of polyethylene glycol (PEG) decorated pharmaceuticals cause accelerated blood clearance (ABC) due to the generation of antibodies reactive to the PEG moiety. Using molecular imaging to monitor response to therapy could be complicated by the ABC effect due to PEG chains in microbubble lipid shells. Our objective was to measure the half-life of targeted contrast flowing through non-tumor tissue during longitudinal imaging studies, and to determine which targeted agent returned the highest signal intensity within tumors. The molecular imaging signals from contrast agents targeted to three distinct molecular targets, Secreted Frizzled-Related Protein-2 (SFRP2), Vascular Endothelial Growth Factor Receptor-2 (VEGFR2), AlphaVBeta3 Integrin (avb3) were all significantly correlated to contrast half-life. The molecular imaging signal from SFRP2 remained significantly higher than the signal returned by ultrasound contrast targeted to either VEGFR2 or avb3 before and after restricting analyses to imaging exams with similar half-lives. We hypothesize that increasing immune clearance rates during our longitudinal studies limited the amount of targeted contrast able to perfuse tumor vasculature, and that this resulted in a global dose-dependent decrease in molecular imaging signals. Molecular imaging may underestimate biomarker levels as longitudinal studies progress and as contrast half-lives decrease, unless contrast dosing is normalized by the amount of contrast able to reach the tumor and surrounding tissue rather than by the injected dosage.