title: An improved imaging agent for malignant melanoma, based on [Nle4,D-Phe7]alpha-melanocyte stimulating hormone.
abstract: 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.
authors.affiliation: Strangeways Research Laboratory, Cambridge, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Bard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005069:Evaluation Studies as Topic; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000493:pharmacokinetics / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000201:enzymology; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: C097971:DTPA bis((Nle(4)-Phe(7))-alpha-MSH); D007205:Indium Radioisotopes; D009363:Neoplasm Proteins; C097943:alpha-MSH, DTPA-Nle(4)-Phe(7)-; D004369:Pentetic Acid; D009074:Melanocyte-Stimulating Hormones; D014442:Monophenol Monooxygenase