Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Ultrasound, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, China.
Contrast Media Mol Imaging. 2018 Mar 8;2018:8710862. doi: 10.1155/2018/8710862. eCollection 2018.
Contrast-enhanced ultrasound imaging has been widely used in the ultrasound diagnosis of a variety of tumours with high diagnostic accuracy, especially in patients with hepatic carcinoma, while its application is rarely reported in thyroid cancer. The currently used ultrasound contrast agents, microbubbles, cannot be targeted to molecular markers expressed in tumour cells due to their big size, leading to a big challenge for ultrasound molecular imaging. Phase-changeable perfluorocarbon nanoparticles may resolve the penetrability limitation of microbubbles and serve as a promising probe for ultrasound molecular imaging.
65 thyroid tumour samples and 40 normal samples adjacent to thyroid cancers were determined for SHP2 expression by IHC. SHP2-targeted PLGA nanoparticles (NPs-SHP2) encapsulating perfluoropentane (PFP) were prepared with PLGA-PEG as a shell material, and their specific target-binding ability was assessed in vitro and in vivo, and the effect on the enhancement of ultrasonic imaging induced by LIFU was studied in vivo.
In the present study, we verified that tumour overexpression of SHP2 and other protein tyrosine phosphatases regulated several cellular processes and contributed to tumorigenesis, which could be introduced to ultrasound molecular imaging for differentiating normal from malignant thyroid diagnostic nodes. The IHC test showed remarkably high expression of SHP2 in human thyroid carcinoma specimens. In thyroid tumour xenografts in mice, the imaging signal was significantly enhanced by SHP2-targeted nanoparticles after LIFU induction.
This study provides a basis for preclinical exploration of ultrasound molecular imaging with NPs-SHP2 for clinical thyroid nodule detection to enhance diagnostic accuracy.
超声造影已广泛应用于多种肿瘤的超声诊断，具有较高的诊断准确性，尤其在肝癌患者中。然而，其在甲状腺癌中的应用报道较少。目前使用的超声造影剂微泡由于体积较大，不能靶向肿瘤细胞表达的分子标志物，这给超声分子成像带来了很大的挑战。相变型全氟碳纳米颗粒可以克服微泡的通透性限制，有望成为超声分子成像的一种有前途的探针。
采用免疫组化法检测 65 例甲状腺肿瘤标本和 40 例甲状腺癌旁正常组织中 SHP2 的表达。采用 PLGA-PEG 作为壳材料，制备靶向 SHP2 的 PLGA 纳米颗粒（NPs-SHP2），包封全氟戊烷（PFP），并评估其在体外和体内的特异性靶向结合能力，以及对 LIFU 诱导的超声成像增强效果的影响。
本研究证实了 SHP2 和其他蛋白酪氨酸磷酸酶在肿瘤中的过度表达调节了多种细胞过程，并促进了肿瘤的发生，这可被引入到超声分子成像中，用于区分正常和恶性甲状腺诊断节点。免疫组化检测显示，人甲状腺癌标本中 SHP2 表达显著增高。在小鼠甲状腺肿瘤异种移植模型中，LIFU 诱导后，靶向 SHP2 的纳米颗粒显著增强了成像信号。
本研究为临床甲状腺结节检测中应用 NPs-SHP2 进行超声分子成像的临床前探索提供了依据，以提高诊断准确性。
