The purpose of this study was to examine and compare the
melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7-
triazacyclononane-1,4,7-triacetic
acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and (64)Cu-DOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7,10-tetraazacyclononane-1,4,7,10-tetraacetic
acid-GGNle-CycMSH(hex)}. Two
lactam bridge-cyclized
peptides,
NOTA-GGNle-CycMSH(hex) and
DOTA-GGNle-CycMSH(hex), were synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The melanocortin-1 (
MC1) receptor binding affinity of
NOTA-GGNle-CycMSH(hex) was determined in B16/F1
melanoma cells and compared with
DOTA-GGNle-CycMSH(hex). The
melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) and (64)Cu-DOTA-GGNle-CycMSH(hex) were determined in B16/F1
melanoma-bearing C57 mice.
NOTA-GGNle-CycMSH(hex) and
DOTA-GGNle-CycMSH(hex) displayed comparable
MC1 receptor binding affinities (1.6 vs 2.1 nM). The substitution of
DOTA with
NOTA dramatically increased the
melanoma uptake and decreased the renal and liver uptake of (64)Cu-NOTA-GGNle-CycMSH(hex). The
tumor uptake of (64)Cu-NOTA-GGNle-CycMSH(hex) was between 12.39 ± 1.61 and 12.71 ± 2.68% ID/g at 0.5, 2, and 4 h postinjection. The accumulation of (64)Cu-NOTA-GGNle-CycMSH(hex) activity in normal organs was lower than 1.02% ID/g except for the kidneys 2, 4, and 24 h postinjection. The
tumor/liver uptake ratios of (64)Cu-NOTA-GGNle-CycMSHhex were 17.96, 16.95, and 8.02, whereas the
tumor/kidney uptake ratios of (64)Cu-NOTA-GGNle-CycMSH(hex) were 2.52, 3.60, and 5.74 at 2, 4, and 24 h postinjection, respectively. Greater than 91% of the injected radioactivity cleared through the urinary system by 2 h postinjection. The substitution of
DOTA with
NOTA resulted in a dramatic increase in
melanoma uptake and decrease in renal and liver uptake of (64)Cu-NOTA-GGNle-CycMSH(hex) as compared to (64)Cu-DOTA-GGNle-CycMSH(hex). High
melanoma uptake coupled with low accumulation in nontarget organs suggested (64)Cu-NOTA-GGNle-CycMSH(hex) as a lead radiolabeled
peptide for
melanoma imaging and
therapy.