Abstract | OBJECTIVE: The purpose of this study was to improve the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys(3,4,10), d-Phe(7), Arg(11)]alpha-melanocyte stimulating hormone(3-13) { DOTA-Re(Arg(11))CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. METHODS: A new peptide of DOTA-Re(Glu(2), Arg(11))CCMSH was designed, synthesized and labeled with (90)Y and (177)Lu. Pharmacokinetics of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. RESULTS: (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH exhibited significantly (P<.05) less renal uptake values than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH were 28.16% and 28.81% of those of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH displayed higher tumor-to-kidney uptake ratios than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was 2.28 and 1.69 times of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. The (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH activity accumulation was low in normal organs except for kidney. CONCLUSIONS:
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Authors | Yubin Miao, Darrell R Fisher, Thomas P Quinn |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 33
Issue 6
Pg. 723-33
(Aug 2006)
ISSN: 0969-8051 [Print] United States |
PMID | 16934691
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Radioisotopes
- Radiopharmaceuticals
- Yttrium Radioisotopes
- alpha-MSH
- Lutetium
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Topics |
- Animals
- Kidney
(metabolism)
- Lutetium
- Melanoma
(radiotherapy)
- Mice
- Mice, Inbred C57BL
- Radioisotopes
- Radiopharmaceuticals
(pharmacokinetics)
- Tissue Distribution
- Yttrium Radioisotopes
- alpha-MSH
(analogs & derivatives, pharmacokinetics)
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