Selective Cyclized α-Melanocyte-Stimulating Hormone Derivative with Multiple N-Methylations for Melanoma Imaging with Positron Emission Tomography

摘要

In this study, we designed and evaluated a novel α-melanocyte-stimulating hormone derivative with four N -methylations for melanocortin 1 receptor-targeted melanoma imaging with positron emission tomography (PET). The resulting peptide, DOTA-Pip-Nle~(4)-Cyclo[Asp~(5)-N -Me-His~(6)-d-Phe~(7)-N -Me-Arg~(8)-N -Me-Trp~(9)-N -Me-Lys~(10)]αMSH_(4-10)-NH_(2) (CCZ01099), showed high receptor selectivity, greatly improved stability, and rapid internalization. [~(68)Ga]Ga-CCZ01099 showed clear tumor visualization and excellent tumor-to-normal tissue contrast with PET imaging in a preclinical melanoma model. Therefore, CCZ01099 is a promising compound for imaging and potentially radioligand therapy for melanoma.