title: Positron emission tomography imaging of CD105 expression with a 64Cu-labeled monoclonal antibody: NOTA is superior to DOTA.
abstract: Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of (64)Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of (64)Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that (64)Cu-NOTA-TRC105 exhibited better stability than (64)Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with (64)Cu-labeled TRC105.
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.forename: Jero
authors.initials: J
authors.lastname: Bean
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Leigh
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 / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D000071063:Endoglin; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D003301:Copper Radioisotopes; C064206:ENG protein, human; D000071063:Endoglin; C502004:Eng protein, mouse; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid