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British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Dec;62(6):919–922. doi: 10.1038/bjc.1990.409

A chelating derivative of alpha-melanocyte stimulating hormone as a potential imaging agent for malignant melanoma.

D R Bard 1, C G Knight 1, D P Page-Thomas 1
PMCID: PMC1971552  PMID: 2257220

Abstract

A chelating derivative of alpha-melanocyte stimulating hormone (MSH) has been synthesised, in which two molecules of the hormone are cross-linked by diethylenetriamine pentaacetic acid (DTPA). This compound, bisMSH-DTPA, was equipotent with MSH in an in vitro tyrosinase assay with Cloudman S91 melanoma cells. When DBA/2 mice bearing the same tumour were injected with bisMSH-DTPA labelled with the gamma-emitting isotope indium-111 (111In), the radioactivity became rapidly associated with the melanoma tissue. By 24 h post-injection, radioactivity in tumour tissue was significantly higher (P less than 0.001) than in spleen, lung, brain, eye and skin. Uptake of radioactivity by the tumours was inhibited by a 200-fold molar excess of MSH, whereas uptake by liver, kidney, spleen, lung, brain, eye and skin was unaffected. We conclude that bisMSH-DTPA may offer an alternative to antibody targeting in the imaging of malignant melanoma.

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Selected References

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  1. Castrucci A. M., Hadley M. E., Sawyer T. K., Hruby V. J. Enzymological studies of melanotropins. Comp Biochem Physiol B. 1984;78(3):519–524. doi: 10.1016/0305-0491(84)90090-7. [DOI] [PubMed] [Google Scholar]
  2. Chaturvedi D. N., Hruby V. J., Castrucci A. M., Kreutzfeld K. L., Hadley M. E. Synthesis and biological evaluation of the superagonist [N alpha-chlorotriazinylaminofluorescein-Ser1,Nle4,D-Phe7]-al pha-MSH. J Pharm Sci. 1985 Mar;74(3):237–240. doi: 10.1002/jps.2600740303. [DOI] [PubMed] [Google Scholar]
  3. Chaturvedi D. N., Knittel J. J., Hruby V. J., Castrucci A. M., Hadley M. E. Synthesis and biological actions of highly potent and prolonged acting biotin-labeled melanotropins. J Med Chem. 1984 Nov;27(11):1406–1410. doi: 10.1021/jm00377a005. [DOI] [PubMed] [Google Scholar]
  4. De Wied D., Jolles J. Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects. Physiol Rev. 1982 Jul;62(3):976–1059. doi: 10.1152/physrev.1982.62.3.976. [DOI] [PubMed] [Google Scholar]
  5. Ghanem G. E., Comunale G., Libert A., Vercammen-Grandjean A., Lejeune F. J. Evidence for alpha-melanocyte-stimulating hormone (alpha-MSH) receptors on human malignant melanoma cells. Int J Cancer. 1988 Feb 15;41(2):248–255. doi: 10.1002/ijc.2910410216. [DOI] [PubMed] [Google Scholar]
  6. LERNER A. B., MCGUIRE J. S. Effect of alpha- and betamelanocyte stimulating hormones on the skin colour of man. Nature. 1961 Jan 21;189:176–179. doi: 10.1038/189176a0. [DOI] [PubMed] [Google Scholar]
  7. Lande S., Pawelek J., Lerner A. B., Emanuel J. R. Assay of melanotropic peptides in an in vitro mammalian system. J Invest Dermatol. 1981 Aug;77(2):244–245. doi: 10.1111/1523-1747.ep12480145. [DOI] [PubMed] [Google Scholar]
  8. Larson S. M., Brown J. P., Wright P. W., Carrasquillo J. A., Hellström I., Hellström K. E. Imaging of melanoma with L-131-labeled monoclonal antibodies. J Nucl Med. 1983 Feb;24(2):123–129. [PubMed] [Google Scholar]
  9. Liu M. A., Nussbaum S. R., Eisen H. N. Hormone conjugated with antibody to CD3 mediates cytotoxic T cell lysis of human melanoma cells. Science. 1988 Jan 22;239(4838):395–398. doi: 10.1126/science.3257303. [DOI] [PubMed] [Google Scholar]
  10. Maecke H. R., Riesen A., Ritter W. The molecular structure of indium-DTPA. J Nucl Med. 1989 Jul;30(7):1235–1239. [PubMed] [Google Scholar]
  11. Moerlein S. M., Welch M. J. The chemistry of gallium and indium as related to radiopharmaceutical production. Int J Nucl Med Biol. 1981;8(4):277–287. doi: 10.1016/0047-0740(81)90034-6. [DOI] [PubMed] [Google Scholar]
  12. Pawelek J., Wong G., Sansone M., Morowitz J. Molecular biology of pigment cells. Molecular controls in mammalian pigmentation. Yale J Biol Med. 1973 Dec;46(5):430–443. [PMC free article] [PubMed] [Google Scholar]
  13. Ravid R., Swaab D. F., Van der Woude T. P., Boer G. J. Immunocytochemically stained binding sites for oxytocin and alpha-melanocyte-stimulating hormone in rat brain following ventricular administration. Brain Res. 1986 Aug 6;379(2):404–408. doi: 10.1016/0006-8993(86)90800-0. [DOI] [PubMed] [Google Scholar]
  14. Reckel R. Monoclonal antibodies: clinical applications. Adv Clin Chem. 1989;27:355–415. doi: 10.1016/s0065-2423(08)60187-0. [DOI] [PubMed] [Google Scholar]
  15. Sawyer T. K., Sanfilippo P. J., Hruby V. J., Engel M. H., Heward C. B., Burnett J. B., Hadley M. E. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5754–5758. doi: 10.1073/pnas.77.10.5754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schroff R. W., Foon K. A., Beatty S. M., Oldham R. K., Morgan A. C., Jr Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res. 1985 Feb;45(2):879–885. [PubMed] [Google Scholar]
  17. Shimizu A., Kawashima S. Kinetic study of internalization and degradation of 131I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems. J Biol Chem. 1989 Aug 15;264(23):13632–13638. [PubMed] [Google Scholar]
  18. Siegrist W., Oestreicher M., Stutz S., Girard J., Eberle A. N. Radioreceptor assay for alpha-MSH using mouse B16 melanoma cells+. J Recept Res. 1988;8(1-4):323–343. doi: 10.3109/10799898809048996. [DOI] [PubMed] [Google Scholar]
  19. Solca F., Siegrist W., Drozdz R., Girard J., Eberle A. N. The receptor for alpha-melanotropin of mouse and human melanoma cells. Application of a potent alpha-melanotropin photoaffinity label. J Biol Chem. 1989 Aug 25;264(24):14277–14281. [PubMed] [Google Scholar]
  20. Stephenson S. L., Kenny A. J. The metabolism of neuropeptides. Hydrolysis of peptides by the phosphoramidon-insensitive rat kidney enzyme 'endopeptidase-2' and by rat microvillar membranes. Biochem J. 1988 Oct 1;255(1):45–51. doi: 10.1042/bj2550045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tatro J. B., Atkins M., Mier J. W., Hardarson S., Wolfe H., Smith T., Entwistle M. L., Reichlin S. Melanotropin receptors demonstrated in situ in human melanoma. J Clin Invest. 1990 Jun;85(6):1825–1832. doi: 10.1172/JCI114642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tatro J. B., Reichlin S. Specific receptors for alpha-melanocyte-stimulating hormone are widely distributed in tissues of rodents. Endocrinology. 1987 Nov;121(5):1900–1907. doi: 10.1210/endo-121-5-1900. [DOI] [PubMed] [Google Scholar]
  23. Wilson J. F., Morgan M. A. Plasma concentrations of alpha-melanotropin in the rat during the acquisition and extinction of conditioned avoidance behaviour and during the acquisition of maze learning behaviour. Psychopharmacology (Berl) 1980;68(1):67–72. doi: 10.1007/BF00426652. [DOI] [PubMed] [Google Scholar]

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