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Basic Science Investigations |
-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)[Cys3,4,10,D-Phe7]
-melanocyte–stimulating hormone3–13 (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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