Positron Emission Tomography Imaging of Endometrial Cancer Using Engineered Anti-EMP2 Antibody Fragments

• DOI: 10.1007/s11307-012-0558-y
• Publication Date: 2012-05-14T20:05:08Z
• Authors: Maoyong Fu; Sarah Brewer; Tove Olafsen; Anna M. Wu; Lynn K. Gordon; Jonathan Said; Jonathan Braun; Madhuri Wadehra
• Keywords: Physiology; Oncology and Carcinogenesis; Nude; Clinical Sciences; PET imaging; Immunoglobulin Variable Region; 610; Mice, Nude; Bioengineering; Clinical sciences; Protein Engineering; Cell Line; Mice; 03 medical and health sciences; Uterine Cancer; Epithelial membrane protein-2; Endometrial cancer; Cell Line, Tumor; Animals; Humans; Tissue Distribution; Inbred BALB C; Cancer; Medicine(all); Analysis of Variance; Mice, Inbred BALB C; 0303 health sciences; Tumor; Membrane Glycoproteins; Biomedical and Clinical Sciences; Minibody; 4.1 Discovery and preclinical testing of markers and technologies; Endometrial Neoplasms; Molecular Imaging; 3. Good health; Nuclear Medicine & Medical Imaging; Copper-64; Copper Radioisotopes; Positron-Emission Tomography; Women's Health; Biomedical Imaging; Female; Biotechnology; Research Article

As imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, goal this study is to determine if antibody fragments EMP2 be useful for positive tumors. The normal tissue distribution was evaluated by immunohistochemistry found discretely expressed both mouse human tissues. To detect tumors, a recombinant anti-EMP2 minibody (scFv-hinge-CH3 dimer; 80 kDa) designed recognize common epitope mice humans characterized. In tumor lines, binding induced internalization degradation, prompting need residualizing strategy. Following conjugation DOTA (1,4,7,10-tetraazacyclododecane-N,N′,N′,N′″-tetraacetic acid), radiolabeled with 64Cu (t 1/2 = 12.7 h) as positron emission tomography (PET) agent EMP2-expressing endometrial xenografts. agent, 64Cu-DOTA minibody, achieved high uptake cancer xenografts overexpressing (10.2 ± 2.6, percent injected dose per gram (%ID/g) SD) moderate wild-type HEC1A (6.0 0.1). cases, precise delineation observed from PET images. contrast, low minibodies EMP2-negative (1.9 0.5). This new immune-PET preclinical assessment targeting vivo. It also have value localization therapeutic response patients EMP2-positive malignancies.