期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 30, 页码 12462-12467出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0705347104
关键词
bombesin; copper 64; molecular imaging; PC-3 tumors
资金
- NCI NIH HHS [1 P50-CA103130-01, R01 CA072942, P50 CA103130, R01-CA72942] Funding Source: Medline
Radiolabeled peptides hold promise as diagnostic/therapeutic targeting vectors for specific human cancers. We report the design and development of a targeting vector, [Cu-64-NOTA-8-Aoc-BBN(7-14)]NH2] (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid, 8-Aoc = 8-aminooctanoic acid, and BBN = bombesin), having very high selectivity and affinity for the gastrin-releasing peptide receptor (GRPr). GRPrs are expressed on a variety of human cancers, including breast, lung, pancreatic, and prostate, making this a viable approach toward site-directed localization or therapy of these human diseases. In this study, [NOTA-X-BBN(7-14)NH2] conjugates were synthesized, where X = a specific pharmacokinetic modifier. The IC50 Of [NOTA-8-Aoc-BBN(7-14)NH2 was determined by a competitive displacement cell-binding assay in PC-3 human prostate cancer cells using I-125-[Tyr(4)]-BBN as the displacement ligand. An IC50 of 3.1 +/- 0.5 nM was obtained, demonstrating high binding affinity of [NOTA-8-Aoc-BBN] for the GRPr. [Cu-64-NOTA-X-BBN] conjugates were prepared by the reaction of (CuCl2)-Cu-64 with peptides in buffered aqueous solution. In vivo studies of [Cu-64-NOTA-8-Aoc-BBN(7-14)NH2] in tumor-bearing PC-3 mouse models indicated very high affinity of conjugate for the GRPr. Uptake of conjugate in tumor was 3.58 +/- 0.70% injected dose (ID) per g at 1 h postintra-venous injection (p.i.). Minimal accumulation of radioactivity in liver tissue (1.58 +/- 0.40% ID per g, 1 h p.i.) is indicative of rapid renal-urinary excretion and suggests very high in vivo kinetic stability of [Cu-64-NOTA-8-Aoc-BBN(7-14)NH2] with little or no in vivo dissociation of Cu-64(2+) from the NOTA chelator. Kidney accumulation at 1 h p.i. was 3.79 +/- 1.09% ID per g. Molecular imaging studies in GRPr-expressing tumor models produced high-contrast, high-quality micro-positron-emission tomography images.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据