High-specific activity radiolabeled
melanocortin peptide preparations are necessary for optimal
melanoma imaging due to the relatively low number of melanocortin-1 receptors (MC1-Rs) per
tumor cell. In this study, a one-step synthesis of 62Cu-labeled MC1-R targeting
peptide Re(Arg11)CCMSH was developed, which yielded high specific activity radiolabeled
peptide preparations that required no post-labeling purification.
DOTA and
NOTA conjugated Re(Arg11)CCMSH
peptides were synthesized and examined for 62Cu radiolabeling and cell binding properties. Biodistribution and PET imaging studies were performed to assess the in vivo
tumor targeting and imaging characteristics of the optimal radiolabeled
peptide.
Melanoma cell binding affinities for
NOTA-,
NOTA-GGG-, and
NOTA-GSG- conjugated Re(Arg11)CCMSH were determined to be 1.3×10-9 M, 1.9×10-9 M and 6.0×10-9 M. The 62Cu radiolabeling efficiencies of
DOTA- and
NOTA- conjugated Re(Arg11)CCMSH analogs were 30% and > 98% after 2 min at 24° C, while 0.5 μg of
NOTA-
GGG-peptide could be labeled to > 95% with a maximum specific activity of 138 Ci/μmol.
Tumor uptake of 62Cu- NOTA-GGG-Re(Arg11)CCMSH in B16/F1
melanoma bearing mice was 4.65±0.48% ID/g and 9.43±2.69% ID/g at 20 and 40 min post injection and was visualized by PET imaging. High specific activity 62Cu-NOTA-GGG-Re(Arg11)CCMSH was prepared in a one-step procedure at 24°C in 6 min. 62Cu-NOTA-GGG-Re(Arg11)CCMSH exhibited MC1-R selective binding and rapid
tumor uptake in B16/F1
melanoma bearing mice that was confirmed by PET imaging studies. High specific activity 62Cu from a 62Zn/62Cu generator coupled with simple one step radiolabeling procedures makes 62Cu an attractive
radionuclide for PET imaging of low-density receptor targets.