Robinson Matthew K, Doss Mohan, Shaller Calvin, Narayanan Deepa, Marks James D, Adler Lee P, González Trotter Dinko E, Adams Gregory P
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Cancer Res. 2005 Feb 15;65(4):1471-8. doi: 10.1158/0008-5472.CAN-04-2008.
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 (18)F-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.
正电子发射断层扫描（PET）为多种癌症的诊断/分期及治疗效果评估提供了一种有效的手段。迄今为止，美国食品药品监督管理局批准的唯一用于肿瘤PET的放射性示踪剂是（18）F-氟脱氧葡萄糖，它通过测量葡萄糖积聚来替代恶性活动。已经开发出具有适当靶向特异性和全身清除特性的工程化抗体片段，预计可基于肿瘤相关抗原的表达对癌症进行有效成像。我们评估了一种对HER2受体酪氨酸激酶具有特异性的小型工程化抗体片段（C6.5双抗体）在用碘-124标记时作为PET放射性示踪剂的功能。我们的研究揭示了小鼠肿瘤异种移植模型中HER2依赖性成像，在实验过程中肿瘤与背景信号随时间增加。通过间接方法进行放射性碘化可减弱表达钠/碘同向转运体的组织对放射性碘的摄取，而不影响对肿瘤异种移植进行成像的能力。此外，我们验证了一种使用临床PET/计算机断层扫描仪对小动物模型系统中的肿瘤摄取进行定量的方法；在所有分析的时间点，PET对肿瘤靶向的定量与基于传统尸检的分析结果相关。因此，双抗体可能代表了开发新型PET放射性示踪剂的一种有效分子结构。
