title: Positron emission tomography imaging of tumor angiogenesis with a 66Ga-labeled monoclonal antibody.
abstract: The goal of this study was to develop a (66)Ga-based positron emission tomography (PET) tracer for noninvasive imaging of CD105 expression during tumor angiogenesis, a hallmark of cancer. (66)Ga was produced using a cyclotron with (nat)Zn or isotopically enriched (66)Zn targets. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (66)Ga. No difference in CD105 binding affinity or specificity was observed between TRC105 and NOTA-TRC105 based on flow cytometry analysis. Reactivity of (66)Ga for NOTA, corrected to the end of bombardment, was between 74 and 222 GBq/μmol for both target enrichments with <2 ppb of cold gallium. (66)Ga-labeling was achieved with >80% radiochemical yield. Serial PET imaging revealed that the murine breast cancer 4T1 tumor uptake of (66)Ga-NOTA-TRC105 was 5.9 ± 1.6, 8.5 ± 0.6, and 9.0 ± 0.6% ID/g at 4, 20, and 36 h postinjection, respectively (n = 4). At the last time point, tumor uptake was higher than that of all organs, which gave excellent tumor contrast with a tumor/muscle ratio of 10.1 ± 1.1. Biodistribution data as measured by gamma counting were consistent with the PET findings. Blocking experiment, control studies with (66)Ga-NOTA-cetuximab, as well as ex vivo histology all confirmed the in vivo target specificity of (66)Ga-NOTA-TRC105. Successful PET imaging with high specific activity (66)Ga (>700 GBq/μmol has been achieved) as the radiolabel opens many new possibilities for future PET research with antibodies or other targeting ligands.
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Wisconsin, United States.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.forename: Duane V
authors.initials: DV
authors.lastname: Myklejord
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001943:Breast Neoplasms / Q000175:diagnosis; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D005710:Gallium Radioisotopes