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External Access > PubMed LinkOut
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ISSN Number: 1535-3508
Title: Molecular Imaging
Volume Number: 8
Issue Number: 02
Page Number: 111
Published: 6 time(s) per Year
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Significant upregulation of the integrin αvβ6 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 αvβ6-targeting peptide, bearing either an [18F]fluorobenzoyl prosthetic group ([18F]FBA-PEG-A20FMDV2) or different [64Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG-A20FMDV2). The compounds were evaluated in vitro by enzyme-linked immunosorbent assay (against the integrin αvβ6 and the closely related integrin αvβ3) and by cell labeling (αvβ6-positive DX3puroβ6/αvβ6-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 αvβ6-specific binding (50% inhibitory concentration [IC50](αvβ6) = 3 to 6 nmol/L; IC50(αvβ3) > 10 μmol/L). In vivo, they displayed comparable, preferential uptake for the αvβ6-expressing xenograft over the αvβ6-negative control (> 4:1 ratio at 4 hours postinjection). Whereas [64Cu]Cu-DOTA-PEG-A20FMDV2 resulted in increased levels of radioactivity in the liver, [64Cu]Cu-CB-TE2A-PEG-A20FMDV2 did not. Significantly, both 64Cu-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 αvβ6. Despite identical targeting peptide moiety and largely equal in vitro behavior, both 64Cu-labeled tracers displayed inferior pharmacokinetics, making them in their present form less suitable candidates than the 18F-labeled tracer for in vivo imaging of αvβ6.
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