体内外分析帕尼单抗 F(ab')(2)片段用于 HER1 阳性癌症的分子成像和治疗。
In Vitro and In Vivo Pre-Clinical Analysis of a F(ab')(2) Fragment of Panitumumab for Molecular Imaging and Therapy of HER1 Positive Cancers.
机构信息
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD 20892;
出版信息
EJNMMI Res. 2011 Jun 7;1(1):1. doi: 10.1186/2191-219X-1-1.
BACKGROUND
The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')(2) fragment of panitumumab and to investigate its potential for imaging and radioimmunotherapy.
METHODS
The panitumumab F(ab')(2) was generated by enzymatic pepsin digestion. After the integrity and immunoreactivity of the F(ab')(2) was evaluated, the fragment was radiolabeled. In vivo studies included direct quantitation of tumor targeting and normal organ distribution of the radiolabeled panitumumab F(ab')(2) as well as planar γ-scintigraphy and PET imaging.
RESULTS
The panitumumab F(ab')(2) was successfully produced by peptic digest. The F(ab')(2) was modified with the CHX-A"-DTPA chelate and efficiently radiolabeled with either (111)In or (86)Y. In vivo tumor targeting was achieved with acceptable uptake of radioactivity in the normal organs. The tumor targeting was validated by both imaging modalities with good visualization of the tumor at 24 h.
CONCLUSIONS
The panitumumab F(ab')(2) fragment is a promising candidate for imaging of HER1 positive cancers.
背景
本研究的目的是描述帕尼单抗 F(ab')(2)片段的体外和体内特性，并研究其在成像和放射免疫治疗中的潜力。
方法
通过酶胃蛋白酶消化产生帕尼单抗 F(ab')(2)。在评估 F(ab')(2)的完整性和免疫反应性之后，对片段进行放射性标记。体内研究包括放射性标记的帕尼单抗 F(ab')(2)的肿瘤靶向和正常器官分布的直接定量，以及平面γ闪烁显像和 PET 成像。
结果
成功通过胃蛋白酶消化产生了帕尼单抗 F(ab')(2)。F(ab')(2)与 CHX-A"-DTPA 螯合物结合，并与 (111)In 或 (86)Y 高效标记。通过两种成像方式都实现了肿瘤靶向，放射性在正常器官中的摄取可接受。肿瘤靶向通过 24 小时的良好肿瘤可视化得到了验证。
结论
帕尼单抗 F(ab')(2)片段是成像 HER1 阳性癌症的有前途的候选物。
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