Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 345-354, May 2009

Melanoma imaging using 111In-, 86Y- and 68Ga-labeled CHX-A″-Re(Arg11)CCMSH☆

  • Lihui Wei

      Affiliations

    • Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
    • Current affiliation: MDS Nordion, Ottawa, ON, Canada K2K 1X8.
    • ,
  • Xiuli Zhang

      Affiliations

    • Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
    • Harry S. Truman Veterans Administration Hospital, Columbia, MO 65201, USA
    • ,
  • Fabio Gallazzi

      Affiliations

    • Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
    • ,
  • Yubin Miao

      Affiliations

    • Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
    • Harry S. Truman Veterans Administration Hospital, Columbia, MO 65201, USA
    • Current affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
    • ,
  • Xiaofang Jin

      Affiliations

    • Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
    • ,
  • Martin W. Brechbiel

      Affiliations

    • Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20893, USA
    • ,
  • Heng Xu

      Affiliations

    • Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20893, USA
    • ,
  • Thomas Clifford

      Affiliations

    • Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20893, USA
    • ,
  • Michael J. Welch

      Affiliations

    • Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
    • ,
  • Jason S. Lewis

      Affiliations

    • Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
    • Current affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
    • ,
  • Thomas P. Quinn

      Affiliations

    • Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
    • Harry S. Truman Veterans Administration Hospital, Columbia, MO 65201, USA
    • Corresponding Author InformationCorresponding author. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA. Tel.: +1 573 882 6099; fax: +1 573 882 5635.

Received 19 November 2008; received in revised form 15 December 2008; accepted 5 January 2009. published online 31 March 2009.

Abstract 

Introduction

A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A″-Re(Arg11)CCMSH, which targeted the melanocortin-1 receptor (MC1-R) overexpressed on melanoma cells, was investigated for its biodistribution and tumor imaging properties.

Methods

The metal bifunctional chelator CHX-A″ was conjugated to the melanoma targeting peptide (Arg11)CCMSH and cyclized by Re incorporation to yield CHX-A″-Re(Arg11)CCMSH. CHX-A″-Re(Arg11)CCMSH was labeled with 111In, 86Y and 68Ga, and the radiolabeled peptides were examined in B16/F1 melanoma-bearing mice for their pharmacokinetic as well as their tumor targeting properties using small animal SPECT and PET.

Results

The radiolabeling efficiencies of the 111In-, 86Y- and 68Ga-labeled CHX-A″-Re(Arg11)CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/μg, respectively. Tumor uptake of the 111In-, 86Y- and 68Ga-labeled peptides was rapid with 4.17±0.94, 4.68±1.02 and 2.68±0.69 %ID/g present in the tumors 2 h postinjection, respectively. Disappearance of radioactivity from the normal organs and tissues was rapid with the exception of the kidneys. Melanoma tumors were imaged with all three radiolabeled peptides 2 h postinjection. MC1-R-specific uptake was confirmed by competitive receptor blocking studies.

Conclusions

Melanoma tumor uptake and imaging was exhibited by the 111In-, 86Y- and 68Ga-labeled Re(Arg11)CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A″-Re(Arg11)CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after 111In, 86Y and 68Ga labeling.

Abbreviations: α-MSH, alpha-melanocyte-stimulating hormone, CHX-A″, N-(2-aminoethyl)-trans-1,2-diaminocyclohexane-N,N′,N″-pentaacetic acid, Re(Arg11)CCMSH, [Re(Cys3,4,10), d-Phe7, Arg11]α-MSH3-13, NDP, [Nle4, d-Phe7]α-MSH

Keywords: Melanoma, Imaging, α-MSH, Peptide, CHX-A″

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☆ The authors would like to acknowledge support from the National Cancer Institute P50-103130, R24 CA86307, the NIH Clinical Biodetective Graduate Training Grant R90DK071510 and the Harry S. Truman Veterans Administration Hospital Biomolecular Imaging Center, Columbia, MO, USA. Small animal PET imaging was supported by an NIH/NCI SAIRP grant (R24 CA86060) with additional support from the Small Animal Imaging Core of the Alvin J. Siteman Cancer Center at Washington University and Barnes-Jewish Hospital. The SAIC is supported by an NCI Cancer Center Support Grant P30 CA91842. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

PII: S0969-8051(09)00007-9

doi:10.1016/j.nucmedbio.2009.01.007

Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 345-354, May 2009

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