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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

An improved imaging agent for malignant melanoma, based on [Nle4,D-Phe7]alpha-melanocyte stimulating hormone.

Two compounds have been synthesized based on [Nle4,D-Phe7]alpha-melanocyte stimulating hormone (NDP-MSH) in which either one or two peptide sequences were covalently linked through their N'-termini to a single molecule of diethylenetriamine pentaacetic acid (DTPA). These two compounds (monoNDP-MSH-DTPA and bisNDP-MSH-DTPA, respectively) bound indium-111 (111In) stably and showed hormonal activity as great or greater than alpha-melanocyte stimulating hormone (alpha-MSH). Both compounds were able to target 111In to Cloudman S91 melanomas in DBA2 mice. MonoNDP-MSH-DTPA gave the highest tumour:blood and tumour:tissue ratios and showed least unspecific radioactivity in the liver and kidney. Radioscintigraphy of mice showed good tumour localization of 111In with both compounds, clear images being obtainable within 2 h of injection. Scans with monoNDP-MSH-DTPA showed some kidney and thyroid but no liver radioactivity, whereas bisNDP-MSH-DTPA gave extensive abdominal radioactivity, most of which was associated with the liver and kidneys. MonoNDP-MSH-DTPA was cleared from the tumour much less rapidly and gave more favourable tumour:blood ratios than other alpha-MSH derivatives previously investigated. It is concluded that monoNDP-MSH-DTPA offers promise as a melanoma imaging agent in man.[1]


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