Meenakshi A, Ganesh V, Suresh Kumar R, Siva Kumar N
Department of Biochemical Oncology, Cancer Institute (WIA), Regional Center for Cancer Research and Treatment of Government of India, Adyar, Chennai, India.
Q J Nucl Med. 2003 Jun;47(2):139-44.
Monoclonal antibodies (MAb) directed at the extra cellular domain (ECD) of epidermal growth factor receptor (EGFR) offer a promising strategy for diagnosis and therapy of cancers that over-express EGFR. Radiolabelled MAbs against cell surface antigens have improved in vivo tumor diagnosis and treatment. EGFR over-expression has been reported in a wide range of carcinomas especially of the head and neck, breast, etc., and is associated with poor prognosis and resistance to therapy. CIBCNSH3 is a murine MAb generated to the ECD of EGFR in our laboratory and has been extensively characterized and has proven antitumor activity. The tumor targeting potential of (99m)Tc labelled CIBCNSH3 in an experimental tumor model is discussed in this paper.
A431, an epidermoid carcinoma cell line with overexpression of EGFR, SUDHLH, a lymphoma cell line was used to induce xenografts in inbred adult female BALB/C mice and used for the study. A reduction mediated method of (99m)Tc labelling was adopted to label the MAb. Scintiscan pictures were taken at different time intervals after i.v. administration of the (99m)Tc labelled MAb using a gamma camera and results were correlated with those of biodistribution studies.
Immunoscan pictures taken at different time periods showed high uptake of the radioimmunoconjugate by the tumor providing clear tumor images and no uptake in control animals with lymphoma xenografts. Results of scan pictures correlated well with the biodistribution studies.
The radioimmunoconjugate (99m)Tc-CIBCNSH3 appears to be a promising tool in identifying any early recurrence and micro-metastasis of lesions that overexpress EGFR.
针对表皮生长因子受体(EGFR)细胞外结构域(ECD)的单克隆抗体(MAb)为过表达EGFR的癌症诊断和治疗提供了一种有前景的策略。针对细胞表面抗原的放射性标记单克隆抗体改善了体内肿瘤的诊断和治疗。据报道,EGFR在多种癌中过表达,尤其是头颈部癌、乳腺癌等,并且与预后不良和治疗耐药相关。CIBCNSH3是我们实验室制备的针对EGFR ECD的鼠单克隆抗体,已得到广泛表征并证明具有抗肿瘤活性。本文讨论了(99m)Tc标记的CIBCNSH3在实验性肿瘤模型中的肿瘤靶向潜力。
使用过表达EGFR的表皮样癌细胞系A431、淋巴瘤细胞系SUDHLH在近交成年雌性BALB/C小鼠中诱导异种移植瘤并用于研究。采用还原介导的(99m)Tc标记方法标记单克隆抗体。静脉注射(99m)Tc标记的单克隆抗体后,在不同时间间隔使用γ相机拍摄闪烁扫描图像,并将结果与生物分布研究结果相关联。
在不同时间段拍摄的免疫扫描图像显示,放射性免疫缀合物在肿瘤中摄取高,提供了清晰的肿瘤图像,而在淋巴瘤异种移植对照动物中无摄取。扫描图像结果与生物分布研究结果相关性良好。
放射性免疫缀合物(99m)Tc-CIBCNSH3似乎是识别过表达EGFR病变的任何早期复发和微转移的有前景的工具。