title: Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.
abstract: The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.
authors.affiliation: College of Pharmacy, ‡Cancer Research and Treatment Center, and §Department of Dermatology, University of New Mexico , Albuquerque, New Mexico 87131, United States.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Flook
authors.forename: Jianquan
authors.initials: J
authors.lastname: Yang
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
mesh_terms: D000818:Animals; D004151:Dipeptides; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D008810:Mice, Inbred C57BL; D015609:Organotechnetium Compounds; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D000521:alpha-MSH / Q000031:analogs & derivatives*; D015091:beta-Alanine / Q000378:metabolism
chemical_list: D004151:Dipeptides; D015609:Organotechnetium Compounds; D044102:Receptor, Melanocortin, Type 1; D015091:beta-Alanine; C038047:alanylaspartic acid; D000521:alpha-MSH; D008239:Lysine