90Y和177Lu标记的α-黑素细胞刺激激素肽类似物在小鼠黑色素瘤模型中的肿瘤靶向特性

Tumor-targeting properties of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues in a murine melanoma model.

作者信息

Miao Yubin, Hoffman Timothy J, Quinn Thomas P

机构信息

Department of Internal Medicine, University of Missouri-Columbia, 65211, USA.

出版信息

Nucl Med Biol. 2005 Jul;32(5):485-93. doi: 10.1016/j.nucmedbio.2005.03.007.

DOI:10.1016/j.nucmedbio.2005.03.007

PMID:15982579

Abstract

UNLABELLED

The purpose of this study was to compare the tumor-targeting properties of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH in a murine melanoma mouse model.

METHODS

The in vitro properties of cellular internalization and retention of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice.

RESULTS

(90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH were 25.70 +/- 4.64 and 14.48 +/- 0.85 %ID/g at 2 h, and 14.09 +/- 2.73 and 17.68 +/- 3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney.

CONCLUSIONS

High tumor-targeting properties of (90)Y-DOTA-Re(Arg(11))CCMSH and (177)Lu-DOTA-Re(Arg(11))CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.

摘要

未标记

本研究的目的是在小鼠黑色素瘤模型中比较（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH的肿瘤靶向特性。

方法

在B16/F1小鼠黑色素瘤细胞中研究了（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH的细胞内化和滞留的体外特性。在荷B16/F1黑色素瘤的C57小鼠中测定了（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH的药代动力学。

结果

（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH在B16/F1细胞中表现出快速的细胞内化和延长的细胞滞留。在荷B16/F1肿瘤的C57小鼠中证实了（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH具有高受体介导的肿瘤摄取和滞留以及快速的全身清除。注射后2小时，（90）Y-DOTA-Re（Arg（11））CCMSH和（177）Lu-DOTA-Re（Arg（11））CCMSH的肿瘤摄取分别为25.70±4.64和14.48±0.85 %ID/g，4小时时分别为14.09±2.73和17.68±3.32 %ID/g。除肾脏外，正常器官中几乎没有活性积聚。