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

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 ^99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg¹¹)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-(Arg¹¹)CCMSH (2), RVD-β-Ala-(Arg¹¹)CCMSH (3), RAD-β-Ala-(Arg¹¹)CCMSH (4), NAD-β-Ala-(Arg¹¹)CCMSH (5), and EAD-β-Ala-(Arg¹¹)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their ^99mTc-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 ^99mTc-peptides. ^99mTc-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 ^99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using ^99mTc-4 as an imaging probe.