99mTc‐labeled tetramer and pentamer of single‐domain antibody for targeting epidermal growth factor receptor in xenografted tumors. (28th April 2016)

• Record Type: Journal Article
• Authors: Li, Chongjiao; Feng, Hongyan; Xia, Xiaotian; Wang, Lifei; Gao, Bin; Zhang, Yongxue; Lan, Xiaoli
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 59:Number 8(2016)
• Page Start: 305
• Page End: 312
• Publication Date: 2016-04-28
• Subjects: protein multimerization -- eosinophil cationic protein -- antibody -- EGFR‐coamplified and over‐expressed protein -- Single‐Photon Emission Computed Tomography; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3399
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : The single‐domain antibody EG2 can be fused with right‐handed coiled‐coil (RHCC) and human cartilage oligomeric matrix protein (COMP), to form the multivalent antibodies EG2‐RHCC and EG2‐COMP. We labeled these two antibodies with 99m Tc and assessed their targeting efficiency for epidermal growth factor receptor (EGFR). Cell binding, uptake, efflux, and blocking studies were performed with EGFR high‐ and/or low‐expressing cells with 99m Tc‐labeled EG2‐RHCC or EG2‐COMP. Single photon‐emission computed tomography (SPECT) imaging and biodistribution studies were further carried out. Both 99m Tc‐EG2‐RHCC and 99m Tc‐EG2‐COMP can specially bind to EGFR in vitro . SPECT imaging showed that A431, which expresses high levels of EGFR, was clearly visible 6 h after 99m Tc‐EG2‐COMP injection; however, it was not detectable after administration of 99m Tc‐EG2‐RHCC. Uptake of both antibodies by the non‐EGFR‐secreting OCM‐1 tumors was low. EG2‐COMP shows promise in identifying EGFR over‐expression in tumors; however, EG2‐RHCC may not be suitable for targeting EGFR in vivo . Abstract : The single‐domain antibody EG2 can be fused with RHCC and COMP, to form the multivalent antibodies EG2‐RHCC and EG2‐COMP. We labeled these two antibodies with 99m Tc and assessed their targeting efficiency. Although 99m Tc‐EG2‐RHCC can specially bind to EGFR, it was not detected in EGFR‐positive A431 tumors post‐injection. 99m Tc‐EG2‐COMP can specially bind to EGFR in vitro and in vivo studies. EG2‐RHCC may not be suitable for targeting EGFR, but EG2‐COMP shows promise in identifying EGFR over‐expression in tumors.