Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide
Significant upregulation of the integrin α v β 6 has been described as a prognostic indicator in several cancers, making it an attractive target for tumor imaging. This study compares variants of a PEGylated α v β 6 -targeting peptide, bearing either an [>18F]fluorobenzoyl prosthetic group ([ 18...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2009-03-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2009.00015 |
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| author | Sven H. Hausner David L. Kukis M. Karen J. Gagnon Catherine E. Stanecki Riccardo Ferdani John F. Marshall Carolyn J. Anderson Julie L. Sutcliffe |
| author_facet | Sven H. Hausner David L. Kukis M. Karen J. Gagnon Catherine E. Stanecki Riccardo Ferdani John F. Marshall Carolyn J. Anderson Julie L. Sutcliffe |
| author_sort | Sven H. Hausner |
| collection | DOAJ |
| description | Significant upregulation of the integrin α v β 6 has been described as a prognostic indicator in several cancers, making it an attractive target for tumor imaging. This study compares variants of a PEGylated α v β 6 -targeting peptide, bearing either an [>18F]fluorobenzoyl prosthetic group ([ 18 F]FBA-PEG-A20FMDV2) or different [ 64 Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG-A20FMDV2). The compounds were evaluated in vitro by enzyme-linked immunosorbent assay (against the integrin α v β 6 and the closely related integrin α v β 6 ) and by cell labeling (α v β 6 -positive DX3puroβ6/α v β 6 -negative DX3puro) and in vivo using micro-positron emission tomography in a mouse model bearing paired DX3puroβ6/Dx3puro xenografts. In vitro, all three compounds showed excellent α v β 6 -specific binding (50% inhibitory concentration [IC 50 ](α v β 6 ) = 3 to g nmol/L; IC 50 (α v β 3 ) > 10 (μmol/L). In vivo, they displayed comparable, preferential uptake for the α v β 6 -expressmg xenograft over the α v β 6 -negative control (> 4:1 ratio at 4 hours postinjection). Whereas [ 64 Cu]Cu-DOTA-PEG-A20FMDV2 resulted in increased levels of radioactivity in the liver, [ 64 Cu]Cu-CB-TE2A-PEG-A20FMDV2 did not. Significantly, both 64 Cu-labeled tracers showed unexpectedly high and persistent levels of radioactivity in the kidneys (> 40% injected dose/g at 4 and 12 hours postinjection). The findings underscore the potential influence of the prosthetic group on targeted in vivo imaging of clinically relevant markers such as α v β 6 . Despite identical targeting peptide moiety and largely equal in vitro behavior, both 64 Cu-labeled tracers displayed inferior pharmacokinetics, making them in their present form less suitable candidates than the 18 F-labeled tracer for in vivo imaging of α v β 6 |
| format | Article |
| id | doaj-art-6f6b4575e93d469e99ad93a943a6c830 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2009-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-6f6b4575e93d469e99ad93a943a6c8302025-01-02T22:39:33ZengSAGE PublishingMolecular Imaging1536-01212009-03-01810.2310/7290.2009.0001510.2310_7290.2009.00015Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific PeptideSven H. HausnerDavid L. KukisM. Karen J. GagnonCatherine E. StaneckiRiccardo FerdaniJohn F. MarshallCarolyn J. AndersonJulie L. SutcliffeSignificant upregulation of the integrin α v β 6 has been described as a prognostic indicator in several cancers, making it an attractive target for tumor imaging. This study compares variants of a PEGylated α v β 6 -targeting peptide, bearing either an [>18F]fluorobenzoyl prosthetic group ([ 18 F]FBA-PEG-A20FMDV2) or different [ 64 Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG-A20FMDV2). The compounds were evaluated in vitro by enzyme-linked immunosorbent assay (against the integrin α v β 6 and the closely related integrin α v β 6 ) and by cell labeling (α v β 6 -positive DX3puroβ6/α v β 6 -negative DX3puro) and in vivo using micro-positron emission tomography in a mouse model bearing paired DX3puroβ6/Dx3puro xenografts. In vitro, all three compounds showed excellent α v β 6 -specific binding (50% inhibitory concentration [IC 50 ](α v β 6 ) = 3 to g nmol/L; IC 50 (α v β 3 ) > 10 (μmol/L). In vivo, they displayed comparable, preferential uptake for the α v β 6 -expressmg xenograft over the α v β 6 -negative control (> 4:1 ratio at 4 hours postinjection). Whereas [ 64 Cu]Cu-DOTA-PEG-A20FMDV2 resulted in increased levels of radioactivity in the liver, [ 64 Cu]Cu-CB-TE2A-PEG-A20FMDV2 did not. Significantly, both 64 Cu-labeled tracers showed unexpectedly high and persistent levels of radioactivity in the kidneys (> 40% injected dose/g at 4 and 12 hours postinjection). The findings underscore the potential influence of the prosthetic group on targeted in vivo imaging of clinically relevant markers such as α v β 6 . Despite identical targeting peptide moiety and largely equal in vitro behavior, both 64 Cu-labeled tracers displayed inferior pharmacokinetics, making them in their present form less suitable candidates than the 18 F-labeled tracer for in vivo imaging of α v β 6https://doi.org/10.2310/7290.2009.00015 |
| spellingShingle | Sven H. Hausner David L. Kukis M. Karen J. Gagnon Catherine E. Stanecki Riccardo Ferdani John F. Marshall Carolyn J. Anderson Julie L. Sutcliffe Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide Molecular Imaging |
| title | Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide |
| title_full | Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide |
| title_fullStr | Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide |
| title_full_unstemmed | Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide |
| title_short | Evaluation of [Cu]Cu-DOTA and [Cu]Cu-CB-TE2A Chelates for Targeted Positron Emission Tomography with an αβ-Specific Peptide |
| title_sort | evaluation of cu cu dota and cu cu cb te2a chelates for targeted positron emission tomography with an αβ specific peptide |
| url | https://doi.org/10.2310/7290.2009.00015 |
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