18F-Labeled Cyclized α-Melanocyte-Stimulating Hormone Derivatives for Imaging Human Melanoma Xenograft with Positron Emission Tomography

摘要

Since metastatic melanoma is deadly, early diagnosis thereof is crucial for managing the disease. We recently developed α-melanocyte-stimulating hormone (αMSH) derivatives, [sup68/supGa]Ga-CCZ01048 and [sup18/supF]CCZ01064, that target the melanocortin 1 receptor (MC1R) for mouse melanoma imaging. In this study, we aim to evaluate [sup18/supF]CCZ01064 as well as a novel dual-ammoniomethyl-trifluoroborate (AmBFsub3/sub) derivative, [sup18/supF]CCZ01096, for targeting human melanoma xenograft using μPET imaging. The peptides were synthesized on solid phase using Fmoc chemistry. Radiolabeling was achieved in a one-step sup18/supF-sup19/supF isotope-exchange reaction. μPET imaging and biodistribution studies were performed in NSG mice bearing SK-MEL-1 melanoma xenografts. The MC1R density on the SK-MEL-1 cell line was determined to be 972?±?154 receptors/cell (n?=?4) via saturation assays. Using [sup18/supF]CCZ01064, moderate tumor uptake (3.05?±?0.47%ID/g) and image contrast were observed?at 2 h post-injection. Molar activity was determined to play a key role. CCZ01096 with two AmBFsub3/sub motifs showed comparable sub-nanomolar binding affinity to MC1R and much higher molar activity. This resulted in improved tumor uptake (6.46?±?1.42%ID/g) and image contrast (tumor-to-blood and tumor-to-muscle ratios were 30.6?±?5.7 and 85.7?±?11.3, respectively)?at 2 h post-injection. [sup18/supF]CCZ01096 represents a promising αMSH-based μPET imaging agent for human melanoma and warrants further investigation for potential clinical translation.