Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Contrast Media Mol Imaging. 2018 May 3;2018:7832805. doi: 10.1155/2018/7832805. eCollection 2018.
Vascular cell adhesion molecule 1 (VCAM-1) is overexpressed in varieties of cancers. This study aimed to evaluate the application of a single chain variable fragment (scFv) of anti-VCAM-1 antibody labeled with Tc as a possible imaging agent in several tumors. VCAM-1 scFv was labeled with Tc using succinimidyl 6-hydrazinium nicotinate hydrochloride, and Tc-HYNIC-VCAM-1 was successfully synthesized with a high radiolabeling yield. VCAM-1 expression was evaluated in six cell lines by immunofluorescence staining. In vitro binding assays showed different binding affinities of Tc-HYNIC-VCAM-1 in different tumor cell lines, with high uptake in B16F10 melanoma and HT1080 fibrosarcoma cells, which was consistent with immunofluorescence staining results. In vivo SPECT planar imaging demonstrated that B16F10 and HT1080 tumors could be clearly visualized. Less intense uptake was observed in human SKOV3.ip ovarian tumor, and weak uptake was observed in human A375m melanoma, MDA-MB-231 breast cancer, and 786-O renal tumors. These findings were confirmed by biodistribution and immunofluorescence studies. High uptake by B16F10 tumors was inhibited by excess unlabeled VCAM-1. Tc-HYNIC-VCAM-1, which selectively binds to VCAM-1, can provide a qualitative and semiquantitative method for noninvasive evaluation of VCAM-1 expression by tumors.
血管细胞黏附分子 1（VCAM-1）在多种癌症中过度表达。本研究旨在评估抗 VCAM-1 单链抗体片段（scFv）与 Tc 标记作为几种肿瘤潜在成像剂的应用。使用琥珀酰亚胺 6-肼基烟酰胺盐酸盐将 VCAM-1 scFv 标记为 Tc，成功合成了具有高放射标记产率的 Tc-HYNIC-VCAM-1。通过免疫荧光染色评估了 VCAM-1 在六种细胞系中的表达。体外结合实验表明，Tc-HYNIC-VCAM-1 在不同肿瘤细胞系中的结合亲和力不同，在 B16F10 黑色素瘤和 HT1080 纤维肉瘤细胞中摄取量较高，与免疫荧光染色结果一致。体内 SPECT 平面成像显示 B16F10 和 HT1080 肿瘤可以清晰显示。在人 SKOV3.ip 卵巢肿瘤中观察到摄取量较低，在人 A375m 黑色素瘤、MDA-MB-231 乳腺癌和 786-O 肾肿瘤中观察到摄取量较弱。这些发现通过生物分布和免疫荧光研究得到了证实。B16F10 肿瘤的高摄取被过量未标记的 VCAM-1 抑制。Tc-HYNIC-VCAM-1 选择性结合 VCAM-1，可提供一种定性和半定量方法，用于非侵入性评估肿瘤 VCAM-1 的表达。
