Evaluation of the human melanoma targeting properties of radiolabeled α-melanocyte stimulating hormone peptide analogues
Evaluation of the human melanoma targeting properties of radiolabeled α-melanocyte stimulating hormone peptide analogues
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DOI：
10.1021/bc034069i
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发表时间：
2003-11-01
影响因子：
4.7
通讯作者：
Quinn, TP
中科院分区：
文献类型：
--
作者：
Miao, YB;Whitener, D;Quinn, TP
本研究的目的是评价两种金属环化α-MSH多肽类似物Re-188-(Arg(11))CCMSH和Re-188-CCMSH对人MC1受体介导的黑色素瘤的靶向性。最初，在一组人黑色素瘤细胞系上测定了MC-1受体的存在和密度。在这项研究中测试的所有8个人类黑色素瘤细胞株都显示出MC1受体的密度为每细胞900到5700个受体。在体外培养的TXM13人黑色素瘤移植SCID小鼠模型上，评价了Re-188-(Arg(11))CCMSH和Re-188-CCMSH的受体亲和力和生物分布特性。生物分布结果显示，Re-188-(Arg(11))CCMSH在注射后1h在肿瘤内蓄积3.06+/-0.68%ID/g，在注射后1h仍有65%以上的活性，在给药后4h仍在肿瘤内。Re-188-(Arg(11))CCMSH的全身清除非常迅速，约82%的注射剂量在注射后4h通过泌尿系统清除。血液和主要器官如肝、肺和肌肉中除肾脏外几乎没有活性。Re-188-CCMSH在TXM13人黑色素瘤移植瘤SCID小鼠体内的肿瘤摄取和滞留与Re-188-(Arg(11))CCMSH相似。而Re-188-CCMSH的肾脏摄取值是Re-188-(Arg(11))CCMSH的两倍。这项研究的结果表明，MC1受体存在于大量人类黑色素瘤细胞的表面，这使得MC1受体成为良好的成像或治疗靶点。此外，Re-188-(Arg(11))CCMSH和Re-188-CCMSH的生物分布特性突出了它们作为人类黑色素瘤治疗剂的潜力。
The purpose of this study was to evaluate the human MC1 receptor-mediated melanoma targeting properties of two metal cyclized alpha-MSH peptide analogues, Re-188-(Arg(11))CCMSH and Re-188-CCMSH. Initially, the presence and density of the MC 1 receptor were determined on a bank of human melanoma cell lines. All eight human melanoma cell lines tested in this study displayed the MC1 receptor at a density of 900 to 5700 receptors per cell. Receptor affinity and biodistribution properties of Re-188-(Arg(11))CCMSH and Re-188-CCMSH were evaluated in a cultured TXM13 human melanoma-xenografted Scid mouse model. Biodistribution results demonstrated that 3.06 +/- 0.68% ID/g of Re-188-(Arg(11))CCMSH accumulated in the tumors 1 h postinjection and greater than 65% of the activity at 1 h postinjection remained in the tumors at 4 h after dose administration. Whole body clearance of Re-188-(Arg(11))CCMSH was very rapid, with approximately 82% of injected dose cleared through urinary system at 4 h postinjection. There was very little activity in blood and major organs such as liver, lung, and muscle except for the kidney. Re-188-CCMSH exhibited similar tumor uptake and retention in TXM13 human melanoma-xenografted Scid mice as Re-188-(Arg(11))CCMSH. However, the kidney uptake value of Re-188-CCMSH was two times higher than that of Re-188-(Arg(11))CCMSH. The results of this study indicate that the MC1 receptor is present on the surface of a large number of human melanoma cells, which makes the MC1 receptor a good imaging or therapeutic target. Moreover, the biodistribution properties of Re-188-(Arg(11))CCMSH and Re-188-CCMSH highlight their potential as therapeutic agents for human melanoma.