Integrin αvβ6-Targeted SPECT Imaging for Pancreatic Cancer Detection
Integrin αvβ6-Targeted SPECT Imaging for Pancreatic Cancer Detection
复制标题
DOI：
10.2967/jnumed.113.132969
复制
发表时间：
2014-06-01
影响因子：
9.3
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Liu, Zhaofei;Liu, Hao;Wang, Fan
整合素α（v）β（6）是整合素家族的成员，在许多恶性肿瘤中特异性表达，但在正常器官中不表达。整合素α（v）β（6）的过度表达通常与恶性潜能和不良预后相关。在这项研究中，我们描述了Tc-99 m标记的整合素α（v）β（6）靶向肽作为SPECT放射性示踪剂的合成和评价，用于整合素α（v）β（6）表达的体内成像。研究方法：将整联蛋白α（v）β（6）-靶向肽（表示为HK肽）与6-肼基烟碱基（HYNIC）缀合，并使用tricine和TPPTS（三苯基膦-3，3 '，3“三磺酸三钠）作为共配体用Tc-99 m进行放射性标记。在BxPC-3（整合素α（v）β（6）-阳性）和HEK 293（整合素α（v）β（6）-阴性）模型中研究了Tc-99 m-HYNIC（tricine）（TPPTS）-HK（Tc-99 m-HHK）的体外和体内特性。采用小动物SPEC/CT评价了Tc-99 m-HHK检测胰腺癌肝转移的能力。结果：Tc-99 m-HHK在体内外均表现出较高的整合素α（v）β（6）结合特异性。Tc-99 m-HHK从血液和除肾脏外的正常器官中迅速清除。在注射后0.5 h观察到BxPC-3肿瘤中Tc-99 m-HHK的最高摄取（0.88 +/-0.12%注射剂量/g）。使用Tc-99 m-HHK获得整合素α（v）β（6）阳性肿瘤的高对比度图像。正常肝组织中最小的非特异性放射性累积呈现高质量的转移病灶SPECT/CT图像。结论：Tc-99 m-HHK是一种很有前途的SPECT显像剂，可用于整合素α（v）β（6）表达的无创显像。99 mTc HHK SPECT/ CT可作为一种有效的方法，用于整合素α（v）β（6）阳性肿瘤原发灶和转移灶的无创性检测。一
lntegrin alpha(v)beta(6), a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin alpha(v)beta(6) is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a Tc-99m-labeled integrin alpha(v)beta(6)-targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin alpha(v)beta(6) expression. Methods: An integrin alpha(v)beta(6)-targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with Tc-99m using tricine and TPPTS (trisodium triphenylphosphine-3,3',3 '' trisulfonate) as coligands. The in vitro and in vivo characteristics of Tc-99m-HYNIC(tricine)(TPPTS)-HK (Tc-99m-HHK) were investigated in BxPC-3 (integrin alpha(v)beta(6)-positive) and HEK293 (integrin alpha(v)beta(6)-negative) models. The ability of Tc-99m-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPEC/CT. Results: Tc-99m-HHK showed high integrin alpha(v)beta(6)-binding specificity both in vitro and in vivo. Tc-99m-HHK was cleared rapidly from the blood and normal organs except for the kidneys. The highest uptake (0.88 +/- 0.12 percentage injected dose per gram) of Tc-99m-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin alpha(v)beta(6)-positive tumors were obtained using Tc-99m-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. Conclusion: Tc-99m-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin alpha(v)beta(6) expression in vivo. SPECT/ CT with Tc-99m-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin alpha(v)beta(6)-positive tumors. a