A comparison of (64)Cu-labeled bi-terminally PEGylated A20FMDV2 peptides targeting integrin α(ν)β(6)

Expression of epithelial-specific integrin α(ν)β(6) is up-regulated in various aggressive cancers and serves as a prognostic marker. Integrin-targeted PET imaging probes have been successfully developed and tested in the clinic. Radiotracers based on the peptide A20FMDV2 derived from foot-and-mouth disease virus represent specific and selective PET ligands for imaging α(ν)β(6)-positive cancers. The present study aims to describe the radiolabeling, in vitro and in vivo evaluation of a bi-terminally PEGylated A20FMDV2 conjugated with DOTA or PCTA for (64)Cu radiolabeling. Stability studies showed radiolabeled complexes remained stable up to 24 h in PBS and human serum. In vitro cell assays in CaSki cervical cancer cells and BxPC-3 pancreatic cancer cells confirmed that the peptides displayed high affinity for α(v)β(6) with K(d) values of ~50 nM. Biodistribution studies revealed that [(64)Cu] Cu-PCTA-(PEG28)(2)-A20FMDV2 exhibited higher tumor uptake (1.63 ± 0.53 %ID/g in CaSki and 3.86 ± 0.58 %ID/g in BxPC-3 at 1 h) when compared to [(64)Cu]Cu-DOTA-(PEG28)(2)-A20FMDV2 (0.95 ± 0.29 %ID/g in CaSki and 2.12 ± 0.83 %ID/g in BxPC-3 at 1 h) . However, higher tumor uptake was accompanied by increased radioactive uptake in normal organs. Therefore, both peptides are appropriate for imaging α(ν)β(6)-positive lesions although further optimization is needed to improve tumor-to-normal-tissue ratios.