Melanoma imaging using (111)In-, (86)Y- and (68)Ga-labeled CHX-A''-Re(Arg11)CCMSH.
BACKGROUND
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.
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lihui
L
Wei
Xiuli
X
Zhang
Fabio
F
Gallazzi
Yubin
Y
Miao
Xiaofang
X
Jin
Martin W
MW
Brechbiel
Heng
H
Xu
Thomas
T
Clifford
Michael J
MJ
Welch
Jason S
JS
Lewis
Thomas P
TP
Quinn
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003500:Cyclization; D005260:Female; D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D013194:Staining and Labeling; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D015021:Yttrium Radioisotopes; D000521:alpha-MSH / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
C487558:Ac-Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Lys-Pro-Val-NH2; D002614:Chelating Agents; D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D010446:Peptide Fragments; D044102:Receptor, Melanocortin, Type 1; D015021:Yttrium Radioisotopes; C542155:alpha-MSH(3-13), N-(2-aminoethyl)-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid-Re(Cys(3,4,10))-Phe(7)-Arg(11)-; D000521:alpha-MSH