D. Bard
Mar 1, 1995
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Journal
InflammoPharmacology
Abstract
Melanocytes possess cell-surface receptors for the naturally occurring tridecapeptide, α-melanocyte stimulating hormone (α-MSH), and this peptide may be used to target imaging or therapeutic agents to malignant melanoma. An α-MSH derivative, bisMSH-DTPA, has been shown to target In accurately to melanomas, both in an experimental model and in a clinical trial. Whilst bisMSH-DTPA also showed high liver and kidney uptake, the specificity of tumour uptake can be markedly improved by the use of unnatural ‘superpotent’ derivatives of α-MSH and by reducing the lipophilicity of the compound. Uptake of the targeted moiety by melanomas may also be increased by creating multiple attachment sites on the α-MSH peptide or by conjugating the peptide to a high-molecular-weight carrier. Other strategies for targeting cytotoxic agents to melanomas using α-MSH have been attempted, including substituting the cytotoxic component for one of the amino acids in the main MSH sequence and creating a fusion protein combining an α-MSH sequence with diphtheria toxin. Whilst an effective α-MSH-based targeted cytotoxic has yet to find acceptance in the clinic, results to date suggest that such an aim is not unrealistic.