Evaluation of the Human Melanoma Targeting Properties of Radiolabeled α-Melanocyte Stimulating Hormone Peptide Analogues

Publisher Website
Google Scholar
Abstract
The purpose of this study was to evaluate the human MC1 receptor-mediated melanoma targeting properties of two metal cyclized α-MSH peptide analogues, 188Re-(Arg11)CCMSH and 188Re-CCMSH. Initially, the presence and density of the MC1 receptor were determined on a bank of human melanoma cell lines. All eight human melanoma cell lines tested in this study displayed the MC1 receptor at a density of 900 to 5700 receptors per cell. Receptor affinity and biodistribution properties of 188Re-(Arg11)CCMSH and 188Re-CCMSH were evaluated in a cultured TXM13 human melanoma-xenografted Scid mouse model. Biodistribution results demonstrated that 3.06 ± 0.68 %ID/g of 188Re-(Arg11)CCMSH accumulated in the tumors 1 h postinjection and greater than 65% of the activity at 1 h postinjection remained in the tumors at 4 h after dose administration. Whole body clearance of 188Re-(Arg11)CCMSH was very rapid, with approximately 82% of injected dose cleared through urinary system at 4 h postinjection. There was very little activity in blood and major organs such as liver, lung, and muscle except for the kidney. 188Re-CCMSH exhibited similar tumor uptake and retention in TXM13 human melanoma-xenografted Scid mice as 188Re-(Arg11)CCMSH. However, the kidney uptake value of 188Re-CCMSH was two times higher than that of 188Re-(Arg11)CCMSH. The results of this study indicate that the MC1 receptor is present on the surface of a large number of human melanoma cells, which makes the MC1 receptor a good imaging or therapeutic target. Moreover, the biodistribution properties of 188Re-(Arg11)CCMSH and 188Re-CCMSH highlight their potential as therapeutic agents for human melanoma.