The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that mediates biological activity through an intracellular tyrosine kinase signaling pathway. This receptor is known to be overexpressed in a variety of human malignancies, and the degree of expression often indicates the clinical outcome for the patient (1). Blocking EGFR activity appears to be an effective approach for the treatment of cancers, and a variety of agents, including monoclonal antibodies (MAb), have been developed for this purpose (2). The human-mouse chimeric MAb C225 was developed to target the EGFR and was demonstrated to inhibit the tyrosine kinase signaling pathway of this receptor. C225 was also shown to inhibit the proliferation of tumor cell lines expressing EGFR (3). This MAb is currently being evaluated in several clinical trials for the treatment of human breast, colon, head and neck, lung, prostate, and cervical cancers (4, 5). However, to determine the possible response of a patient, it is necessary to evaluate the degree of EGFR expression in the tumors by immunohistology before and after the MAb treatment. This is an invasive procedure and, because of tumor heterogeneity and metastasis, some tumors may be inaccessible and may be overlooked during patient evaluation (5). Therefore, a radiochemical targeted to the EGFR would be a useful tool to determine the level of EGFR expression in the tumor cells and could help select patients who are most likely to benefit from MAb therapy (5). Using diethylene triamine pentaacetic acid (DTPA), the radioactive metal chelator indium (In) was linked to C225 and the radiolabeled MAb (In-DTPA-C225) was used in a phase 1 clinical trial to image human squamous cell carcinomas expressing high levels of EGFR (6). As a result of nonspecific uptake of radioactivity, a considerable amount of the radiolabel was detected in the liver of patients undergoing the treatment. A similar observation was made when another MAb against EGFR, MAb 528, was labeled with In using DTPA. This radiolabeled MAb accumulated in the kidneys as well as the liver (7). These studies indicated a limited usefulness of the two radiolabeled MAbs for the detection of tumors and metastasis in the thorax. In an attempt to improve the specificity of radiolabeled C225 uptake, Wen et al. (8) synthesized the MAb conjugated to polyethylene glycol (PEG), along with DTPA, to obtain DTPA-PEG-C225. The conjugated MAb was then radiolabeled with In and evaluated for the detection of xenograft tumors expressing EGFR in nude mice (5).
表皮生长因子受体（EGFR）是一种跨膜糖蛋白，它通过细胞内酪氨酸激酶信号通路介导生物学活性。已知该受体在多种人类恶性肿瘤中过度表达，其表达程度通常预示着患者的临床预后（1）。阻断EGFR活性似乎是治疗癌症的有效方法，为此已开发出多种药物，包括单克隆抗体（MAb）（2）。人鼠嵌合单克隆抗体C225被开发用于靶向EGFR，并被证明可抑制该受体的酪氨酸激酶信号通路。C225还被证明可抑制表达EGFR的肿瘤细胞系的增殖（3）。目前，这种单克隆抗体正在多项治疗人类乳腺癌、结肠癌、头颈癌、肺癌、前列腺癌和宫颈癌的临床试验中进行评估（4, 5）。然而，为了确定患者可能的反应，有必要在单克隆抗体治疗前后通过免疫组织化学评估肿瘤中EGFR的表达程度。这是一种侵入性操作，而且由于肿瘤的异质性和转移，一些肿瘤可能无法触及，在患者评估过程中可能会被忽视（5）。因此，一种靶向EGFR的放射性化学物质将是确定肿瘤细胞中EGFR表达水平的有用工具，并有助于选择最有可能从单克隆抗体治疗中获益的患者（5）。利用二乙三胺五乙酸（DTPA），将放射性金属螯合剂铟（In）与C225连接，放射性标记的单克隆抗体（In-DTPA-C225）被用于一项1期临床试验，以对表达高水平EGFR的人类鳞状细胞癌进行成像（6）。由于放射性的非特异性摄取，在接受治疗的患者肝脏中检测到了大量的放射性标记物。当另一种抗EGFR单克隆抗体MAb 528用DTPA标记铟时，也观察到了类似的现象。这种放射性标记的单克隆抗体在肾脏和肝脏中都有积累（7）。这些研究表明这两种放射性标记的单克隆抗体在检测胸部肿瘤和转移方面的实用性有限。为了提高放射性标记的C225摄取的特异性，Wen等人（8）合成了与聚乙二醇（PEG）以及DTPA偶联的单克隆抗体，以获得DTPA-PEG-C225。然后将偶联的单克隆抗体用铟进行放射性标记，并在裸鼠中评估其对表达EGFR的异种移植肿瘤的检测能力（5）。
