Therapeutic efficacy of a 177Lu-labeled DOTA conjugated alpha-melanocyte-stimulating hormone peptide in a murine melanoma-bearing mouse model.
The aim of this study was to examine the therapeutic efficacy of (177)Lu-DOTA-Re(Arg(11))CCMSH in the B16/F1 murine melanoma-bearing mouse model.


METHODS
(177)Lu-DOTA-Re(Arg(11))CCMSH was prepared in 0.5 M NH(4)OAc at a pH of 5.4. Two (2) treatment groups of 10 melanoma-bearing C57 mice were administrated with 2 x 18.5 MBq and 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH through the tail vein, respectively. One (1) group of 10 melanoma-bearing C57 mice was injected with saline placebos as untreated melanoma-bearing controls.


RESULTS
In contrast to the untreated melanoma-bearing control group, (177)Lu-DOTA-Re(Arg(11))CCMSH administration yielded rapid and lasting therapeutic effects in the treatment groups. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment decreased the tumor growth rate and significantly (p > 0.05) prolonged the survival time of melanoma-bearing C57 mice. Treatment with 2 x 18.5 MBq or 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH significantly extended the mean survival of tumor-bearing mice from 13.3 to 15.1 and 16.2 days, respectively. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment produced no observed acute renal toxicity.


CONCLUSIONS
The therapy study results revealed that (177)Lu-DOTA-Re(Arg(11))CCMSH yielded quantitative therapeutic effects in B16/F1 melanoma-bearing mice and appeared to be a promising radiolabeled peptide for the targeted radionuclide therapy of melanoma.
Miao
Yubin
Y
College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
Shelton
Tiffani
T
Quinn
Thomas P
TP
D000818:Animals; D001120:Arginine; D002614:Chelating Agents; D004195:Disease Models, Animal; D006573:Heterocyclic Compounds, 1-Ring; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008187:Lutetium / Q000627:therapeutic use* / Q000633:toxicity; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D051379:Mice; D011859:Radiography; D011868:Radioisotopes; D016019:Survival Analysis; D000521:alpha-MSH / Q000627:therapeutic use*
D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000521:alpha-MSH; D008187:Lutetium; D001120:Arginine