title: Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence.
abstract: The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and (64)Cu to yield (64)Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of (64)Cu-NOTA-TRC105-800CW was 11.9 ± 1.2, 13.9 ± 3.9, and 13.4 ± 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with (64)Cu-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of (64)Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal.
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Room 7137, 1111 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Tapas R
authors.initials: TR
authors.lastname: Nayak
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.forename: Duane V
authors.initials: DV
authors.lastname: Myklejord
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001557:Benzenesulfonates; D001943:Breast Neoplasms / Q000473:pathology*; D003301:Copper Radioisotopes; D000071063:Endoglin; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008156:Luciferases; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000503:physiopathology* / Q000556:secondary*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001557:Benzenesulfonates; D003301:Copper Radioisotopes; D000071063:Endoglin; C502004:Eng protein, mouse; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C562366:IRDye 800CW; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D008156:Luciferases; C579557:carotuximab