体内
微气泡
分子成像
免疫疗法
癌症研究
靶向治疗
显像剂
医学
癌症
病理
化学
超声波
生物
内科学
放射科
生物技术
作者
Udaya Kumar,Arutselvan Natarajan,Tarik F. Massoud,Ramasamy Paulmurugan
标识
DOI:10.1016/j.jconrel.2022.04.030
摘要
PD-L1 (programmed death-ligand 1) targeted therapies may be useful for several cancers. The use of non-invasive diagnostic and prognostic molecular imaging platforms could improve clinical assessment of PD-L1 tumor status during these therapies. Contrast enhanced ultrasound molecular imaging (CE-USMI) techniques may offer versatile and cost-effective ways to detect and quantify the expression levels of cellular targets in vivo. However, conventional use of microbubbles as a blood pool contrast agent for CE-USMI is limited to accessing intravascular biomarkers rather than reflecting the tumor molecular status. Using a microfluidic based reconstruction process we therefore developed ultra-stable nanobubbles (NBs) as a contrast agent for molecular imaging of vascular and extravascular cell surface markers. We then functionalized these NBs by covalently linking to nanobody (FN3hPD-L1) targeting human (h)PD-L1 to measure the expression of human PD-L1 in the tumor microenvironment (TME) in vivo. We showed the specific binding of hPD-L1 targeted NBs in cell culture, and in xenografted mouse models of hPD-L1 expressing CT26 tumors. CE-USMI of hPD-L1 in the TME in vivo showed ~3-fold increase in contrast signal compared to non-targeted NBs. Overall, in vivo use of CE-USMI with hPD-L1 targeted NBs has the potential for clinical translation and imaging of human cancers during immunotherapy, and for prognostic evaluation of patient response to PD-L1 targeted immunotherapy.
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