Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha-MSH peptide

Abstract

The purpose of this study was to determine the metastatic melanoma imaging property of 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}. HYNIC-Aoc-Nle-CycMSHhex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The IC50 value of HYNIC-Aoc-Nle-CycMSHhex was 0.78 ± 0.13 nM for B16/F10 melanoma cells. 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex displayed significantly higher uptake (14.26 ± 2.74 and 10.45 ± 2.31% ID/g) in B16/F10 metastatic melanoma-bearing lung than that in normal lung (0.90 ± 0.15 and 0.53 ± 0.14% ID/g) at 2 and 4 h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex as an imaging probe at 2 h post-injection, underscoring its potential as an imaging probe for metastatic melanoma detection.

68 Ga-DOTA-GGNle-CycMSH hex targets the melanocortin-1 receptor for melanoma imaging

“…PET images showed substantial uptake of 68 Ga-DOTA-GGNle-CycMSH hex in B16/F10 pulmonary metastatic melanoma lesions. In our previous work, we demonstrated the success of SPECT imaging of B16/F10 pulmonary melanoma metastases using 99m Tc- and 67 Ga-labeled lactam-cyclized α-MSH peptides as imaging probes (34, 36). The difference in imaging quality between SPECT and PET images in this B16/F10 pulmonary metastatic melanoma model was likely attributed to the lower resolution of animal PET as compared to animal SPECT.…”

PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma

“…While the rates of melanoma diagnosis continue to be alarming, molecularly targeted approaches, including inhibition of immune checkpoints such as programmed death-1 receptor (PD-1) have significantly improved patient outcomes over the last decade. Nivolumab, a Food and Drug Administration-approved antibody directed at PD-1 inhibition enhanced median overall survival in patients with metastatic melanoma (6). PD-1 binds to ligands PD-L1 or PD-L2 to act as an inhibitory immune checkpoint, negatively regulating immune cell activation and effector function (5,7,8).…”