Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

ObjectiveThe purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys3,4,10, d-Phe7, Arg11]α-melanocyte stimulating hormone3–13 {DOTA-Re(Arg11)CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence.MethodsA new peptide of DOTA-Re(Glu2, Arg11)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice.Results90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH exhibited significantly (P<.05) less renal uptake values than 90Y- and 177Lu-DOTA-Re(Arg11)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-Re(Arg11)CCMSH, respectively, at 4 h postinjection. 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH displayed higher tumor-to-kidney uptake ratios than 90Y- and 177Lu-DOTA-Re(Arg11)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH was 2.28 and 1.69 times of 90Y- and 177Lu-DOTA-Re(Arg11)CCMSH, respectively, at 4 h postinjection. The 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH activity accumulation was low in normal organs except for kidney.ConclusionsCoupling 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 90Y- and 177Lu-DOTA-Re(Glu2, Arg11)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.