Evaluation of [ 64Cu]Cu-DOTA and [ 64Cu]Cu-CB-TE2A chelates for targeted positron emission tomography with an α vβ 6-Specific peptide

Julie Sutcliffe, Sven H. Hausner, David L. Kukis, M. Karen J Gagnon, Catherine E. Stanecki, Riccardo Ferdani, John F. Marshall, Carolyn J. Anderson

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Significant upregulation of the integrin α vβ 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 vβ 6-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 α vβ 6 and the closely related integrin α vβ 3) and by cell labeling (α v6-positive DX3puroP6/α vβ 6-negative DX3puro) and in vivo using micro-positron emission tomography in a mouse model bearing paired DX3puroP6/Dx3puro xenografts. In vitro, all three compounds showed excellent α vβ 6-specific binding (50% inhibitory concentration [IC 50](α vβ 6) = 3 to 6 nmol/L; IC 50vβ 3) > 10 Hmol/L). In vivo, they displayed comparable, preferential uptake for the α vβ 6-expressing xenograft over the α vβ 6-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 <α vβ 6. 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 α vβ 3.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalMolecular Imaging
Issue number2
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Condensed Matter Physics


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