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

Abstract

INTRODUCTION:

A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A''-Re(Arg(11))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 (Arg(11))CCMSH and cyclized by Re incorporation to yield CHX-A''-Re(Arg(11))CCMSH. CHX-A''-Re(Arg(11))CCMSH was labeled with (111)In, (86)Y and (68)Ga, 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 (111)In-, (86)Y- and (68)Ga-labeled CHX-A''-Re(Arg(11))CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/microg, respectively. Tumor uptake of the (111)In-, (86)Y- and (68)Ga-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 (111)In-, (86)Y- and (68)Ga-labeled Re(Arg(11))CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A''-Re(Arg(11))CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after (111)In, (86)Y and (68)Ga labeling.

• Authors: Lihui Wei, Xiuli Zhang, Fabio Gallazzi, Yubin Miao, Xiaofang Jin, Martin W Brechbiel, Heng Xu, Thomas Clifford, Michael J Welch, Jason S Lewis, Thomas P Quinn
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 36 Issue 4 Pg. 345-54 (May 2009) ISSN: 1872-9614 [Electronic] United States
• PMID: 19423001 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Ac-Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Lys-Pro-Val-NH2
• Chelating Agents
• Gallium Radioisotopes
• Indium Radioisotopes
• Peptide Fragments
• Receptor, Melanocortin, Type 1
• Yttrium Radioisotopes
• alpha-MSH(3-13), N-(2-aminoethyl)-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid-Re(Cys(3,4,10))-Phe(7)-Arg(11)-
• alpha-MSH

Topics

• Animals
• Chelating Agents (chemistry)
• Cyclization
• Female
• Gallium Radioisotopes
• Indium Radioisotopes
• Melanoma (diagnostic imaging, metabolism)
• Mice
• Peptide Fragments (chemistry, metabolism, pharmacokinetics)
• Positron-Emission Tomography
• Receptor, Melanocortin, Type 1 (metabolism)
• Staining and Labeling
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon
• Yttrium Radioisotopes
• alpha-MSH (chemistry, metabolism, pharmacokinetics)