Gallium-67-labeled lactam bridge-cyclized α-melanocyte stimulating hormone peptide for primary and metastatic melanoma imaging

The purpose of this study was to examine the melanoma imaging properties of a novel ⁶⁷Ga-labeled lactam bridge-cyclized α-melanocyte stimulating hormone (α-MSH) peptide. A lactam bridge-cyclized R-MSH peptide, DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly- Arg-Pro-Val-Asp]}, was synthesized and radiolabeled with ⁶⁷Ga. The melanoma targeting and pharmacokinetic properties of ⁶⁷Ga-DOTA- GlyGlu-CycMSH were determined in B16/F1 flank primary melanoma-bearing and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. Flank primary melanoma and pulmonary metastatic melanoma imaging were performed by small animal single photon emission computed tomography (SPECT)/CT using ⁶⁷Ga-DOTA- GlyGlu-CycMSH as an imaging probe. ⁶⁷Ga-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. ⁶⁷Ga- DOTA-GlyGlu-CycMSH exhibited substantial tumor uptake (12.93 ± 1.63%ID/g at 2 h postinjection) and prolonged tumor retention (5.02 ± 1.35%ID/g at 24 h postinjection) in B16/F1 melanomabearing C57 mice. The uptake values for nontarget organs were generally low (<0.30%ID/g) except for the kidneys at 2, 4, and 24 h postinjection. ⁶⁷Ga-DOTA-GlyGlu-CycMSH exhibited significantly (p < 0.05) higher uptakes (1.44 ± 0.75%ID/g at 2 h postinjection and 1.49 ± 0.69%ID/g at 4 h postinjection) in metastatic melanoma-bearing lung than those in normal lung (0.15 ± 0.10%ID/g and 0.17 ± 0.11%ID/g at 2 and 4 h postinjection, respectively). Both flank primary B16/F1 melanoma and B16/F10 pulmonary melanoma metastases were clearly visualized by SPECT/CT using ⁶⁷Ga-DOTA-GlyGlu-CycMSH as an imaging probe 2 h postinjection. ⁶⁷Ga-DOTAGlyGlu-CycMSH exhibited favorable melanoma targeting and imaging properties, highlighting its potential as an effective imaging probe for early detection of primary and metastatic melanoma.