Biologically Active Monoiodinated α-MSH Derivatives for Receptor Binding Studies Using Human Melanoma Cells

Eberlé, Alex N.; Verin, Vreni Jäggin; Solca, Flavio; Siegrist, Walter; Küenlin, Caroline; Bagutti, Claudia; Stutz, Sibylla; Girard, J.

doi:10.3109/10799899109066410

Cited by 39 publications

(19 citation statements)

References 7 publications

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“…The tracer was purified in 2 steps on a reversed-phase mini-column (Spherisorb ODS/10 pm; Phase Separation, Nonvalk, CT), using a step-wise gradient of 1% TFAimethanol, and then by reversed-phase HPLC, as described (Siegrist et al, 1989;Eberle et al, 1991). This leads to mono-iodinated [1251]-a-MSH with a specific activity of 2200 Ci/mmol.…”

Section: Preparation Of [Iz5i]-a-mshmentioning

confidence: 99%

[111In]-DTPA-labeled analogues of α-melanocyte-stimulating hormone for melanoma targeting: Receptor bindingin vitro andin vivo

et al. 1994

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Six alpha-MSH(4-10) [Nle-Asp-His-D-Phe-Arg-Trp-Lys-amide] derivatives carrying 2 or 1 or no 2,3-dihydroxy-(2S)-propyl (DHP) groups on the Lys10 amino side chain were coupled to diethylene-triaminopentaacetic acid (DTPA, a chelator for 111In) in monomeric and dimeric forms and tested for their binding activity and bioactivity in vitro with mouse and human melanoma cell lines and by receptor autoradiography to tumor sections, as well as in vivo with normal and melanoma-bearing mice: DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10),DTPA-[Nle4, Asp5, D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10), DTPA[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10), DTPA-bis-([Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10)), DTPA-bis[([Nle4,Asp5,D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10)) and DTPA-bis-([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)). In the receptor-binding assays with B16-F1 mouse and D10 human melanoma cells, the KD values ranged between 0.76 and 31.17 nM and in the melanin bioassay the results were similar (EC50 values between 0.15 and 4.40 nM). The tissue distribution of the 111In-labeled compounds in C57Bl/6J mice showed that the dimeric [111In]-DTPA-bis([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)) and the monomeric [111In]-DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10) exhibited the lowest non-specific binding. In mice carrying B16-F1 melanoma tumors, the monomeric compound displayed 2-fold higher 111In uptake by the tumor and a much lower non-specific uptake by the liver (12-fold) and the kidneys (2.5-fold) than the dimeric derivative. This demonstrates that modification of the Lys10 side chain by DHP is a promising lead for new MSH radiopharmaceuticals for melanoma targeting.

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Section: Preparation Of [Iz5i]-a-mshmentioning

confidence: 99%

[111In]-DTPA-labeled analogues of α-melanocyte-stimulating hormone for melanoma targeting: Receptor bindingin vitro andin vivo

et al. 1994

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“…Peptides that target the MC1-R and melanin were labeled with beta-particle-emitting radionuclides 188 Re [27][28][29][30][31][32], 90 Y [33], 177 Lu [33,34], 64 Cu [35][36][37], alphaparticle-emitters 212 Pb/ 212 Bi [38] and Auger-emitter 125 I [ [39][40][41][42][43]. While the therapeutic properties of 111 In-labeled somatostatin peptides have been examined in preclinical [44,45] and clinical [46,47] studies, it is likely that nuclear localization and trapping may be necessary for optimal effectiveness in cancer treatment [48].…”

Section: Selection Criteria For Therapeutic Radionuclidesmentioning

confidence: 99%

Peptide-targeted radionuclide therapy for melanoma

Miao

Quinn

2008

Critical Reviews in Oncology/Hematology

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Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1-R and melanin. The promising therapeutic efficacies of 188Re-(Arg(11))CCMSH (188Re-[Cys(3,4,10), D-Phe(7),Arg(11)]-alpha-MSH(3-13)), 177Lu- and 212Pb-labeled DOTA-Re(Arg(11))CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys(3,4,10), D-Phe(7), Arg(11))]-alpha-MSH(3-13)) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end-stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy.

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“…The wells were washed six more times with PBS, covered, and stored at 4°C until use for RIA. Salmon MCH was iodinated by using the chloramine T method, and the tracer was purified on C18 minicolumns, as described previously (Eberle et al, 1991). Dried HPLC fractions were dissolved in 200 µl of RIA buffer (50 mM Na-phosphate, pH 7.5; 0.9% NaCl; 0.1% BSA; 0.01% Na-azide) and incubated with 50 µl of tracer (5,000 cpm) in the antiserum-coated wells at 4°C for 24 hours.…”

Section: Radioimmunoassaymentioning

confidence: 99%

Melanin-concentrating hormone system in the brain of the lungfishProtopterus annectens

et al. 1998

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The neurochemical anatomy of the lungfish brain is of particular interest, because many features in these animals might be representative of the common ancestor of land vertebrates. In the present study, we have investigated the localization and biochemical characteristics of melanin-concentrating hormone (MCH)-immunoreactive material in the central nervous system of the African lungfish, Protopterus annectens. The most prominent group of MCH-immunoreactive cell bodies was found in the dorsal hypothalamus. Additional groups of MCH-immunoreactive perikarya were detected in the telencephalon within the medial and dorsal pallium, the medial subpallium, and the ventral part of the lateral subpallium. Brightly immunofluorescent nerve fibers were seen in the anterior olfactory nucleus, the ventral part of the medial pallium, the medial subpallium, and the anterior preoptic area. In the diencephalon, the hypothalamus and the medial region of the dorsal thalamus exhibited a dense accumulation of fibers. MCH-immunoreactive fibers were also found in the tectum and the tegmentum of the mesencephalon and within the reticular formation of the rhombencephalon. In the pituitary, several small groups of cells of the intermediate lobe showed a bright fluorescence. Reversed-phase high-performance liquid chromatography (HPLC) analysis of diencephalon and pituitary extracts resolved a major MCH-immunoreactive peak that coeluted with synthetic salmon MCH. The distribution of MCH in the brain of P. annectens suggests that, in lungfishes, this peptide may exert neuromodulator or neurotransmitter functions. The presence of MCH-like immunoreactivity in the intermediate lobe of the pituitary indicates that, in dipnoans, MCH may also act as a typical pituitary hormone.

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Biologically Active Monoiodinated α-MSH Derivatives for Receptor Binding Studies Using Human Melanoma Cells

Cited by 39 publications

References 7 publications

[111In]-DTPA-labeled analogues of α-melanocyte-stimulating hormone for melanoma targeting: Receptor bindingin vitro andin vivo

[111In]-DTPA-labeled analogues of α-melanocyte-stimulating hormone for melanoma targeting: Receptor bindingin vitro andin vivo

Peptide-targeted radionuclide therapy for melanoma

Melanin-concentrating hormone system in the brain of the lungfishProtopterus annectens

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