title: Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues.
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
  Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.
authors.affiliation: Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211, USA. ymiao@salud.unm.edu
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D007668:Kidney / Q000378:metabolism*; D008187:Lutetium; D008545:Melanoma / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000521:alpha-MSH; D008187:Lutetium