111In-Labeled Lactam Bridge-Cyclized α-Melanocyte Stimulating Hormone Peptide Analogues for Melanoma Imaging
详细信息 查看全文
- 作者：Yubin Miao ; Fabio Gallazzi ; Haixun Guo ; Thomas P. Quinn
- 刊名：Bioconjugate Chemistry
- 出版年：2008
- 出版时间：February 2008
- 年：2008
- 卷：19
- 期：2
- 页码：539 - 547
- 全文大小：433K
- 年卷期：v.19,no.2(February 2008)
- ISSN：1520-4812
文摘
The purpose of this study was to examine the influence of the lactam bridge cyclization on melanoma targeting and biodistribution properties of the radiolabeled conjugates. Two novel lactam bridge-cyclized α-MSH peptide analogues, DOTA-CycMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]) and DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]), were synthesized and radiolabeled with 111In. The internalization and efflux of 111In-labeled CycMSH peptides were examined in B16/F1 melanoma cells. The melanoma targeting properties, pharmacokinetics, and SPECT/CT imaging of 111In-labeled CycMSH peptides were determined in B16/F1 melanoma-bearing C57 mice. Both 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH exhibited fast internalization and extended retention in B16/F1 cells. The tumor uptake values of 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH were 9.53 ± 1.41% injected dose/gram (% ID/g) and 10.40 ± 1.40% ID/g at 2 h postinjection, respectively. Flank melanoma tumors were clearly visualized with 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH by SPECT/CT images at 2 h postinjection. Whole-body clearance of the peptides was fast, with greater than 90% of the radioactivities cleared through urinary system by 2 h postinjection. There was low radioactivity (<0.8% ID/g) accumulated in blood and normal organs except kidneys at all time points investigated. Introduction of a negatively charged linker (-Gly-Glu-) into the peptide sequence decreased the renal uptake by 44% without affecting the tumor uptake at 4 h postinjection. High receptor-mediated melanoma uptakes coupled with fast whole-body clearance in B16/F1 melanoma-bearing C57 mice demonstrated the feasibility of using 111In-labeled lactam bridge-cyclized α-MSH peptide analogues as a novel class of imaging probes for receptor-targeting melanoma imaging.