Structural Assessment and Biological Evaluation of Two N3S Bombesin Derivatives

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• 作者：Eleni Gourni ; Penelope Bouziotis ; Dimitra Benaki ; George Loudos ; Stavros Xanthopoulos ; Maria Paravatou-Petsotas ; Maria Mavri-Vavagianni ; Maria Pelecanou ; Spyros C. Archimandritis ; Alexandra D. Varvarig
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：July 23, 2009
• 年：2009
• 卷：52
• 期：14
• 页码：4234-4246
• 全文大小：942K
• 年卷期：v.52,no.14(July 23, 2009)
• ISSN：1520-4804

文摘

The aim of the present study is the evaluation of the ^99mTc complexes of two bombesin-like peptides: Gly1′-Gly2′-Cys3′-Aca-BN[2−14] (BN-1.1) and Gly1′-Gly2′-Cys3′-Aca-BN[7−14] (BN-1.1p). The BN derivatives were synthesized according to the solid phase peptide synthesis method, and characterized by ESI-MS and NMR. ^185/187Re-BN-1.1 and ^185/187Re-BN-1.1p were also identified by ESI-MS and NMR. The ^99mTc complexes were stable over time in human plasma, while they degraded rapidly in kidney−liver homogenates. The peptides and their ^99mTc complexes showed high affinity for the human GRP receptors expressed in PC-3 cells. The rate of internalization of these radiolabeled biomolecules was found to be time-dependent. Also, it was found that there was no long-term retention of the radioactive metabolites into the cells. Tissue distribution of the radiopeptides was evaluated in normal mice and in prostate cancer experimental models. Significant uptake of radioactivity was observed in the pancreas of PC-3 tumor-bearing SCID mice. Dynamic studies of both radiopeptides showed satisfactory tumor images.