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

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

Yubin Miao, PhD¹^,2, Nellie K. Owen, DVM³, Darrell R. Fisher, PhD⁴, Timothy J. Hoffman, PhD²^,5 and Thomas P. Quinn, PhD¹^,3

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

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FIGURE 1. Structure of ¹⁸⁸ReO-(Arg¹¹) CCMSH: Ac-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH₂.

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FIGURE 2. Melanoma imaging of ¹⁸⁸Re-(Arg¹¹)CCMSH in B16/F1 murine melanoma-bearing C57 mice. Planar ${gamma}$ -camera images were collected 4 h (left) and 18 h (right) after administration of ¹⁸⁸Re-(Arg¹¹)CCMSH.

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FIGURE 3. Effect of ¹⁸⁸Re-(Arg¹¹)CCMSH treatment on growth rate of B16/F1 murine melanoma tumors. Mice were implanted with B16/F1 tumor cells on day 0 and treated with ¹⁸⁸Re-(Arg¹¹)CCMSH on day 4. Tumor measurements were performed daily starting 24 h after administration of 7.4 MBq (•), 22.2 MBq ( ${diamondsuit}$ ), and 2 x 14.8 MBq ( ${blacksquare}$ ) of ¹⁸⁸Re-(Arg¹¹)CCMSH or saline placebo ( ${blacktriangleup}$ ). Second 14.8-MBq dose was given on day 7.

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FIGURE 4. Survival analysis of B16/F1 murine melanoma-bearing C57 mice. Kaplan–Meier survival curves for B16/F1 murine melanoma-bearing mice treated with 7.4 MBq ( ${blacktriangledown}$ ), 22.2 MBq ( ${blacktriangleup}$ ), and 2 x 14.8 MBq ( ${blacksquare}$ ) of ¹⁸⁸Re-(Arg¹¹)CCMSH or saline placebo ( ${square}$ ). Mean survival time was 9.4 ± 1.1 d for untreated control group, 10.2 ± 1.0 d (P > 0.05) for group treated with 7.4 MBq, 10.3 ± 1.3 d (P > 0.05) for group treated with 22.2 MBq, and 13.3 ± 1.9 d (P < 0.05) for group treated with 2 x 14.8 MBq.

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FIGURE 5. Effect of ¹⁸⁸Re-(Arg¹¹)CCMSH treatment on growth rate of TXM13 human melanoma tumors. Measurable TXM13 tumors were obtained on day 0 and treated with ¹⁸⁸Re-(Arg¹¹)CCMSH on day 4. Tumor measurements were performed twice a week starting 4 d after administration of 22.2 MBq ( ${blacktriangleup}$ ), 2 x 14.8 MBq (•), and 37.0 MBq ( ${blacksquare}$ ) of ¹⁸⁸Re-(Arg¹¹)CCMSH or saline placebo ( ${diamondsuit}$ ). Second 14.8 MBq dose was given on day 18.

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FIGURE 6. Survival analysis of TXM13 human melanoma-bearing SCID mice. Kaplan–Meier survival curves for TXM13 human melanoma-bearing mice treated with 22.2 MBq ( ${blacktriangleup}$ ), 2 x 14.8 MBq ( ${blacksquare}$ ), and 37.0 MBq ( ${blacktriangledown}$ ) of ¹⁸⁸Re-(Arg¹¹)CCMSH or saline placebo ( ${square}$ ). Mean survival time was 39.6 ± 15.0 d for untreated control group, 41.4 ± 10.9 d (P > 0.05) for 2 x 14.8-MBq treated group, 57.6 ± 24.2 d (P < 0.05) for 22.2-MBq treated group, and 72.7 ± 18.3 d (P < 0.05) for 37.0-MBq treated group.

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

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