Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.
Hematology and Oncology, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2017 Dec;80(12):766-773. doi: 10.1016/j.jcma.2017.02.010. Epub 2017 Sep 29.
Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive indium (In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent In-cetuximab and investigate the biological distribution of In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts.
We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the In-cetuximab was investigated and compared for imaging small (50 mm) and large (250 mm) tumor of CRC xenografts, respectively.
The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the In-cetuximab bound to tumor specifically that was higher than that in other organs.
We suggested that the In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.
结直肠癌（CRC）中表皮生长因子受体（EGFR）的过度表达是开发抗肿瘤治疗药物的肿瘤靶标。西妥昔单抗是一种针对 EGFR 阳性肿瘤的抗 EGFR 单克隆抗体，可抑制细胞增殖和生长，本研究中用放射性铟（In）标记用于诊断 EGFR 阳性 CRC。本研究旨在评估非侵入性核成像剂 In-西妥昔单抗的疗效，并研究 In-西妥昔单抗在 HCT-15 诱导的 EGFR 阳性 CRC 肿瘤异种移植中的生物分布。
我们将西妥昔单抗与同位素螯合剂二乙烯三胺五乙酸（DTPA）偶联，然后用 In 标记西妥昔单抗-DTPA，并通过即时薄层层析（iTLC）测量标记效率。此外，分别研究并比较了 In-西妥昔单抗对大小为 50mm 和 250mm 的 CRC 异种移植肿瘤的成像。
通过 MALDI-TOF-MS 测量，西妥昔单抗与 DTPA 的偶联比为 1:6。计算并实验了用 10mCi In 标记西妥昔单抗的最佳标记浓度为 48μg，iTLC 检测标记效率>80%。结果表明，作为一种可靠的非侵入性诊断剂，In-西妥昔单抗在两种大小的肿瘤中均有积累，而在大肿瘤中肿瘤与肌肉的比值为 7.5 倍。生物分布数据表明，In-西妥昔单抗与肿瘤特异性结合，高于其他器官。
我们建议，In-西妥昔单抗有望在进一步的临床实践中用于早期诊断和预测 EGFR 阳性 CRC 的预后。
