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Therapeutic Efficacy of a ¹⁸⁸Re-Labeled -Melanocyte–Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

¹ Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri
² Department of Internal Medicine, University of Missouri-Columbia, Columbia, Missouri
³ Department of Radiology, University of Missouri-Columbia, Columbia, Missouri
⁴ Pacific Northwest National Laboratory, Richland, Washington
⁵ Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri

The purpose of this study was to examine the therapeutic efficacy of ¹⁸⁸Re-(Arg¹¹)[Cys^3,4,10,D-Phe⁷]-melanocyte–stimulating hormone_3–13 (CCMSH) in the B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models. Methods: (Arg¹¹)CCMSH was synthesized and labeled with ¹⁸⁸Re to form ¹⁸⁸Re-(Arg¹¹)CCMSH. B16/F1 melanoma-bearing mice were administrated 7.4 MBq, 22.2 MBq, and 2 x 14.8 MBq of ¹⁸⁸Re-(Arg¹¹)CCMSH via the tail vein. TXM13 melanoma-bearing mice were separately injected with 22.2 MBq, 2 x 14.8 MBq, and 37.0 MBq of ¹⁸⁸Re-(Arg¹¹)CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, ¹⁸⁸Re-(Arg¹¹)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2 x 14.8 MBq of ¹⁸⁸Re-(Arg¹¹)CCMSH significantly extended the mean life of B16/F1 tumor mice (P < 0.05), whereas the mean life of TXM13 tumor mice was significantly prolonged after treatment with 22.2-MBq and 37.0- MBq doses of ¹⁸⁸Re-(Arg¹¹)CCMSH (P < 0.05). High-dose ¹⁸⁸Re-(Arg¹¹)CCMSH produced no observed normal tissue toxicity. Conclusion: The therapy study results revealed that ¹⁸⁸Re-(Arg¹¹)CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models. ¹⁸⁸Re-(Arg¹¹)CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

Key Words: -melanocyte–stimulating hormone • ¹⁸⁸Re-labeled peptide • targeted radionuclide therapy • human melanoma • murine melanoma

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