Molecular targeting of carbonic anhydrase ix in mice with hypoxic HT29 colorectal tumor xenografts Journal Article


Authors: Carlin, S.; Khan, N.; Ku, T.; Longo, V. A.; Larson, S. M.; Smith-Jones, P. M.
Article Title: Molecular targeting of carbonic anhydrase ix in mice with hypoxic HT29 colorectal tumor xenografts
Abstract: Background:Carbonic anhydrase IX (CAIX) is a membrane spanning protein involved in the enzymatic regulation of tumor acid-base balance. CAIX has been shown to be elevated in a number of hypoxic tumor types. The purpose of this study was to determine the efficiency of intact and IgG fragments of cG250 to target CAIX in vivo in a hypoxic tumor model. Methodology/Principal Findings: Conventional biodistribution studies were performed with 111In-DO3A-cG250, 111In-DO3A-F(ab')2-cG250 and 111In-DO3A-Fab-cG250. Additional ex vivo analysis of the tumor was performed with markers for tumor hypoxia, blood perfusion and endogenous CAIX expression. All four data sets were digitally correlated to determine the optimal agent for determining hypoxia in a HT29 colon cancer xenograft. The HT29 human colorectal tumor xenografts show strong CAIX expression in hypoxic areas of poor blood perfusion. The intact IgG had an initial high focal uptake at the periphery of these hypoxic regions and penetration into the areas of highest CAIX expression over the 7-day study period. The lower molecular weight antibody fragments had a faster uptake into areas of high CAIX expression, but had a much lower absolute uptake at the optimal imaging times. Conclusions/Significance:For the clinical detection of hypoxia induced CAIX using cG250 antibody based agents, imaging with the intact IgG at 7 days post injection would allow for the most sensitive and accurate detection of CAIX. © 2010 Carlin et al.
Keywords: controlled study; protein expression; nonhuman; methodology; diagnostic accuracy; sensitivity and specificity; binding affinity; colorectal cancer; mouse; animal; metabolism; animals; mice; animal tissue; mus; protein targeting; animal experiment; animal model; tumor xenograft; drug screening; pathology; xenograft model antitumor assays; molecular imaging; diagnostic imaging; immunoreactivity; vascularization; tumor marker; monoclonal antibody; hypoxia; colorectal neoplasms; antibodies, monoclonal; carbonate dehydratase ix; diagnostic agent; monoclonal antibody g250; isotope labeling; nude mouse; mice, nude; enzyme analysis; colorectal tumor; radioactivity; cell hypoxia; immunofluorescence test; ex vivo study; indium 111; cell strain ht29; molecular weight; ht29 cells; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; carbonate dehydratase; carbonic anhydrases; tumor blood flow; antibody labeling; immunoglobulin f(ab) fragment; carbonic anhydrase ix, mouse; tissue perfusion
Journal Title: PLoS ONE
Volume: 5
Issue: 5
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2010-05-27
Start Page: e10857
Language: English
DOI: 10.1371/journal.pone.0010857
PUBMED: 20523727
PROVIDER: scopus
PMCID: PMC2877709
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "Art. No.: e10857" - "Source: Scopus"
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MSK Authors
  1. Steven M Larson
    784 Larson
  2. Sean Denis Carlin
    81 Carlin
  3. Valerie Ann Longo
    30 Longo
  4. Thomas Ku
    11 Ku
  5. Nahida Khan
    2 Khan