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: D R Bard
• Journal: Nuclear medicine communications (Nucl Med Commun) Vol. 16 Issue 10 Pg. 860-6 (Oct 1995) ISSN: 0143-3636 [Print] England
• PMID: 8570117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DTPA bis((Nle(4)-Phe(7))-alpha-MSH)
• Indium Radioisotopes
• Neoplasm Proteins
• alpha-MSH, DTPA-Nle(4)-Phe(7)-
• Pentetic Acid
• Melanocyte-Stimulating Hormones
• Monophenol Monooxygenase

Topics

• Amino Acid Sequence
• Animals
• Enzyme Activation (drug effects)
• Evaluation Studies as Topic
• Indium Radioisotopes (pharmacokinetics)
• Male
• Melanocyte-Stimulating Hormones (pharmacokinetics, pharmacology)
• Melanoma, Experimental (diagnostic imaging, enzymology)
• Mice
• Mice, Inbred DBA
• Molecular Sequence Data
• Monophenol Monooxygenase (metabolism)
• Neoplasm Proteins (metabolism)
• Neoplasm Transplantation
• Pentetic Acid (analogs & derivatives, pharmacokinetics, pharmacology)
• Radionuclide Imaging
• Tissue Distribution
• Tumor Cells, Cultured