Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-05-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2877709?pdf=render |
| _version_ | 1819195585670938624 |
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| author | Sean Carlin Nahida Khan Thomas Ku Valerie A Longo Steve M Larson Peter M Smith-Jones |
| author_facet | Sean Carlin Nahida Khan Thomas Ku Valerie A Longo Steve M Larson Peter M Smith-Jones |
| author_sort | Sean Carlin |
| collection | DOAJ |
| description | 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.Conventional biodistribution studies were performed with (111)In-DO3A-cG250, (111)In-DO3A-F(ab')(2)-cG250 and (111)In-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.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. |
| first_indexed | 2024-12-23T02:15:06Z |
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| id | doaj.art-9a3ff8d3b1c14ced95be7b58ce0d9a39 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T02:15:06Z |
| publishDate | 2010-05-01 |
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| series | PLoS ONE |
| spelling | doaj.art-9a3ff8d3b1c14ced95be7b58ce0d9a392022-12-21T18:03:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1085710.1371/journal.pone.0010857Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts.Sean CarlinNahida KhanThomas KuValerie A LongoSteve M LarsonPeter M Smith-JonesCarbonic 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.Conventional biodistribution studies were performed with (111)In-DO3A-cG250, (111)In-DO3A-F(ab')(2)-cG250 and (111)In-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.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.http://europepmc.org/articles/PMC2877709?pdf=render |
| spellingShingle | Sean Carlin Nahida Khan Thomas Ku Valerie A Longo Steve M Larson Peter M Smith-Jones Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. PLoS ONE |
| title | Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. |
| title_full | Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. |
| title_fullStr | Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. |
| title_full_unstemmed | Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. |
| title_short | Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts. |
| title_sort | molecular targeting of carbonic anhydrase ix in mice with hypoxic ht29 colorectal tumor xenografts |
| url | http://europepmc.org/articles/PMC2877709?pdf=render |
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