The purpose of this study is to examine the melanocortin-1 receptor (MC1R) targeting and specificity of 203 Pb-DOTA-GGNle-CycMSH hex in melanoma cells and tumors to facilitate its potential therapeutic application when labeled with 212 Pb. The melanocortin-1 receptor (MC1R)specific targeting and imaging properties of 203 Pb-DOTA-GGNle-CycMSH hex were determined on B16/F1 and B16/F10 murine melanoma cells, and in B16/F1 flank melanoma-, B16/F10 flank melanoma-and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. 203 Pb-DOTA-GGNle-CycMSH hex displayed MC1R-specific binding on B16/F1 and B16/F10 melanoma cells and tumors. B16/F1 flank melanoma, B16/F10 flank melanoma and B16/F10 pulmonary metastatic melanoma lesions could be clearly imaged by single photon emission computed tomography (SPECT) using 203 Pb-DOTA-GGNle-CycMSH hex as an imaging probe. The favorable melanoma targeting and imaging properties highlighted the potential of 203 Pb-DOTA-GGNle-CycMSH hex as a MC1R-targeting melanoma imaging probe, and warranted the evaluation of 212 Pb-DOTA-GGNle-CycMSH hex for melanoma therapy in future studies.

Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.