(99m) Tc-labeled tetramer and pentamer of single-domain antibody for targeting epidermal growth factor receptor in xenografted tumors.
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.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.|Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Chongjiao
C
Li
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
Hongyan
H
Feng
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
Xiaotian
X
Xia
CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Life Sciences, University of Science and Technology of China, Hefei, China.
Lifei
L
Wang
CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Life Sciences, University of Science and Technology of China, Hefei, China.|China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Bin
B
Gao
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
Yongxue
Y
Zhang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
Xiaoli
X
Lan
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D011854:Radiochemistry; D061905:Single-Domain Antibodies / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D061905:Single-Domain Antibodies; D013667:Technetium; D066246:ErbB Receptors
EGFR-coamplified and over-expressed protein; Single-Photon Emission Computed Tomography; antibody; eosinophil cationic protein; protein multimerization