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

Abstract

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 v,β 6-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 50(α vβ 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