Quantitative immuno-positron emission tomography imaging oil HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody
Quantitative immuno-positron emission tomography imaging oil HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody
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DOI：
10.1158/0008-5472.can-04-2008
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发表时间：
2005-02-15
期刊：
影响因子：
11.2
通讯作者：
Adams, GP
中科院分区：
文献类型：
--
作者：
Robinson, MK;Doss, M;Adams, GP
正电子发射断层扫描(PET)为多种癌症的诊断/分期和疗效评估提供了有效的手段。到目前为止，美国食品和药物管理局批准的唯一用于肿瘤学PET的放射性示踪剂是F-18-氟脱氧葡萄糖，它测量葡萄糖积累作为恶性活动的替代品。已经开发出具有适当的靶向性和系统消除特性的工程化抗体片段，以允许基于肿瘤相关抗原的表达对癌症进行有效的成像。我们评估了一种针对HER2受体酪氨酸激酶(c6.5diabody)的小的工程抗体片段，当用碘-124标记时，它作为PET放射性示踪剂的能力。我们的研究揭示了HER2依赖的小鼠肿瘤移植瘤的成像，在实验过程中，肿瘤与背景信号的时间依赖增加。通过间接方法进行放射性碘标记可以减少表达Na/I同向转运蛋白的组织对放射性碘的摄取，而不会影响对肿瘤移植瘤进行成像的能力。此外，我们验证了一种在小动物模型系统中使用临床PET/计算机断层扫描仪来量化肿瘤摄取的方法；在分析的所有时间点上，通过PET对肿瘤靶向的量化与传统的基于尸检的分析相关联。因此，二联体可能代表了开发新型PET放射性示踪剂的有效分子结构。
Positron emission tomography (PET) provides an effective means of both diagnosing/staging several types of cancer and evaluating efficacy of treatment. To date, the only U.S. Food and Drug Administration-approved radiotracer for oncologic PET is F-18-fluoro-deoxyglucose, which measures glucose accumulation as a surrogate for malignant activity. Engineered antibody fragments have been developed with the appropriate targeting specificity and systemic elimination properties predicted to allow for effective imaging of cancer based on expression of tumor associated antigens. We evaluated a small engineered antibody fragment specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotracer when labeled with iodine-124. Our studies revealed HER2-dependent imaging of mouse tumor xenografts With a time-dependent increase in tumor-to-background signal over the course of the experiments. Radioiodination via an indirect method attenuated uptake of radioiodine in tissues that express the Na/I symporter Without affecting the ability to image the tumor xenografts. In addition, we validated a method for using a clinical PET/computed tomography scanner to quantify tumor uptake in small-animal model systems; quantitation of the tumor targeting by PET correlated with traditional necropsy-based analysis at all time points analyzed. Thus, diabodies may represent an effective molecular structure for development of novel PET radiotracers.