Document Detail


Positron emission tomography imaging of tumor angiogenesis with a (61/64)Cu-labeled F(ab')(2) antibody fragment.
MedLine Citation:
PMID:  23316869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')(2) fragment of TRC105, a human/murine chimeric IgG1 monoclonal antibody that binds with high avidity to human and murine CD105 (i.e., endoglin), and investigate its potential for positron emission tomography (PET) imaging of tumor angiogenesis after (61/64)Cu-labeling. TRC105-F(ab')(2) of high purity was produced by pepsin digestion of TRC105, which was confirmed by SDS-PAGE, HPLC analysis, and mass spectrometry. (61/64)Cu-labeling of NOTA-TRC105-F(ab')(2) (NOTA denotes 1,4,7-triazacyclononane-1,4,7-triacetic acid) was achieved with yields of >75% (specific activity: ∼115 GBq/μmol). PET imaging revealed rapid tumor uptake of (64)Cu-NOTA-TRC105-F(ab')(2) in the 4T1 murine breast cancer model (5.8 ± 0.8, 7.6 ± 0.6, 5.6 ± 0.4, 5.0 ± 0.6, and 3.8 ± 0.7% ID/g at 0.5, 3, 16, 24, and 48 h postinjection respectively; n = 4). Since tumor uptake peaked at 3 h postinjection, (61)Cu-NOTA-TRC105-F(ab')(2) also gave good tumor contrast at 3 and 8 h postinjection. CD105 specificity of the tracers was confirmed by blocking studies and histopathology. In conclusion, the use of a F(ab')(2) fragment led to more rapid tumor uptake (which peaked at 3 h postinjection) than radiolabeled intact antibody (which often peaked after 24 h postinjection), which may allow for same day immunoPET imaging in future clinical studies.
Authors:
Hao Hong; Yin Zhang; Hakan Orbay; Hector F Valdovinos; Tapas R Nayak; Jero Bean; Charles P Theuer; Todd E Barnhart; Weibo Cai
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-14
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  10     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-08-20     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  709-16     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / chemistry*,  diagnostic use*
Antigens, CD / immunology
Breast Neoplasms / pathology*
Copper / chemistry*
Female
Flow Cytometry
Humans
Intracellular Signaling Peptides and Proteins / immunology
Mice
Neovascularization, Pathologic / pathology*
Positron-Emission Tomography / methods*
Receptors, Cell Surface / immunology
Grant Support
ID/Acronym/Agency:
P30 CA014520/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/ENG protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Receptors, Cell Surface; 0/endoglin protein, mouse; 789U1901C5/Copper
Comments/Corrections

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