AlF-labeled alpha-melanocyte-stimulating hormone (α-MSH) peptide derivative for the early detection of melanoma.

OBJECTIVE

Early detection plays a role in the prognosis of melanoma, the most aggressive skin cancer. Cu- and Ga-labeled alpha-melanocyte-stimulating hormone (α-MSH) analogs targeting the melanocortin-1 receptor are promising positron emission tomography (PET) tracers for detecting melanoma, and the use of F-labeling will further contribute to the detectability and availability. However, the high radiochemistry demand related to the conventional F-labeling methods has restricted the development of F-labeled α-MSH analogs. A recently developed radiofluorination method using aluminum-fluoride (AlF) offers a simple, efficient, and time-saving labeling procedure compared to the conventional F-labeling methods. Herein, we sought to establish a simple preparation method for an F-labeled α-MSH analog using AlF, and we examined its potential for the early detection of melanoma.

METHODS

A 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA)-conjugated α-MSH analog (NOTA-GGNle-CycMSH) was prepared by the Fmoc solid-phase strategy. NOTA-GGNle-CycMSH was labeled with AlF by heating at 105 °C using a microwave synthesizer for 15 min. Biodistribution study was conducted on B16/F10-luc melanoma-bearing mice at 30 min, 1 h and 3 h after injection of AlF-NOTA-GGNle-CycMSH. PET imaging was conducted on melanoma-bearing mice at 1 h post-injection. One day prior to the PET imaging, bioluminescence imaging was also performed.

RESULTS

AlF-NOTA-GGNle-CycMSH was readily prepared with a high radiochemical yield (94.0 ± 2.8%). The biodistribution study showed a high accumulation of AlF-NOTA-GGNle-CycMSH in the tumor at 30 min and 1 h post-injection (6.69 ± 1.49 and 7.70 ± 1.71%ID/g, respectively). The tumor-to-blood ratio increased with time: 3.46 ± 0.89, 12.67 ± 1.29, and 35.27 ± 9.12 at 30 min, 1 h, and 3 h post-injection, respectively. In the PET imaging, AlF-NOTA-GGNle-CycMSH clearly visualized the tumors and depicted very small tumors (< 3 mm).

CONCLUSIONS

We successfully prepared AlF-NOTA-GGNle-CycMSH in a simple and efficient manner. AlF-NOTA-GGNle-CycMSH showed high tumor accumulation and clearly visualized very small tumors in melanoma-bearing mice. These findings suggest that AlF-NOTA-GGNle-CycMSH will be a promising PET tracer for melanoma imaging at an earlier stage.