Substitution of the Lys Linker with the 尾-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated 伪-Melanocyte Stimulating Hormone

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• 作者：Adam M. Flook ; Jianquan Yang ; Yubin Miao
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：November 13, 2014
• 年：2014
• 卷：57
• 期：21
• 页码：9010-9018
• 全文大小：339K
• ISSN：1520-4804

文摘

The purpose of this study was to examine whether the substitution of the Lys linker with the 尾-Ala could reduce the renal uptake of ^99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated 伪-melanocyte stimulating hormone (伪-MSH) peptides. RSD-尾-Ala-(Arg¹¹)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-尾-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH₂}, RTD-尾-Ala-(Arg¹¹)CCMSH (2), RVD-尾-Ala-(Arg¹¹)CCMSH (3), RAD-尾-Ala-(Arg¹¹)CCMSH (4), NAD-尾-Ala-(Arg¹¹)CCMSH (5), and EAD-尾-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 尾-Ala linker dramatically reduced the renal uptake of all six ^99mTc-peptides. ^99mTc-4 exhibited the highest melanoma uptake (15.66 卤 6.19% ID/g) and the lowest kidney uptake (20.18 卤 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.