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

Abstract

The purpose of this study was to evaluate the human MC1 receptor-mediated melanoma targeting properties of two metal cyclized alpha-MSH peptide analogues, (188)Re-(Arg(11))CCMSH and (188)Re-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 (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH were evaluated in a cultured TXM13 human melanoma-xenografted Scid mouse model. Biodistribution results demonstrated that 3.06 +/- 0.68 %ID/g of (188)Re-(Arg(11))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 (188)Re-(Arg(11))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. (188)Re-CCMSH exhibited similar tumor uptake and retention in TXM13 human melanoma-xenografted Scid mice as (188)Re-(Arg(11))CCMSH. However, the kidney uptake value of (188)Re-CCMSH was two times higher than that of (188)Re-(Arg(11))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 (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH highlight their potential as therapeutic agents for human melanoma.

111In-Labeled Lactam Bridge-Cyclized α-Melanocyte Stimulating Hormone Peptide Analogues for Melanoma Imaging

“…The IC 50 values of DOTA-CycMSH and DOTA-GlyGlu-CycMSH were determined by using methods described previously (8). B16/F1 cells were harvested and seeded into a 24-well cell culture plate (5×10 5 In-DOTA-GlyGluCycMSH was injected into each mouse through the tail vein.…”

Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

“…Due to their small size, peptides are also ideal for multiple modifications of nanoparticle constructs and generation of pluripotent nanoparticles. 38 Moreover, α-MSH binds to melanocortin receptors and, in particular, is a potent agonist of the melanocortin type 1 receptor (MCR1, overexpressed by many melanoma cells 39 ) and binds to MCR1 with high affinity (IC 50 0.21 nmol/L). 40 Importantly, more than 80% of human metastatic melanoma samples have been found to display MCR1.…”

Gallium-68-labeled DOTA-rhenium-cyclized α-melanocyte-stimulating hormone analog for imaging of malignant melanoma

“…It has been reported the MC1R expression ranges from several hundred to around 10,000 receptors per cell [29]. In 2003, Miao et al, reported that MC1R receptor expression ranged from nine hundred (1.49 fmol/million SKMEL28 cells) to around six thousand (9.46 fmol/ million TXM13 cells) receptors per cell on human melanoma cells [30], enabling the use of radiolabeled α-MSH peptide analogs as specific melanoma diagnostic and therapeutic agents.…”