TRIUMF, Nuclear Medicine Division, 4004 Wesbrook Mall, Vancouver, Canada BC V6T 2A3.
Bioorg Med Chem Lett. 2013 Jul 1;23(13):3920-6. doi: 10.1016/j.bmcl.2013.04.060. Epub 2013 Apr 30.
Acetylene-bearing 2-[(18)F]fluoropyridines [(18)F]FPy5yne and PEG-[(18)F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [(18)F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6-14) analogues via copper-catalyzed azide-alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing (18)F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated (18)F peptide. Assessment of water-soluble peptide pharmacokinetics and tumour-targeting capabilities in a mouse model of prostate cancer is currently underway.
含乙炔的 2-[(18)F]氟吡啶 [(18)F]FPy5yne 和 PEG-[(18)F]FPyKYNE 是通过其相应的 2-三甲基铵吡啶基前体的高效亲核杂芳环 [(18)F]氟化制备的。通过铜催化的叠氮化物-炔烃环加成偶联将前体与叠氮化物和 PEG3 修饰的蛙皮素(6-14)类似物连接，得到用于胃泌素释放肽受体的 PET 成像的单和二聚-PEG 化配体。与类似的非最小 PEG 化 (18)F 肽相比，PEG3-和 PEG2/PEG3 修饰的 (18)F 肽的亲脂性降低。目前正在进行在前列腺癌小鼠模型中评估水溶性肽药代动力学和肿瘤靶向能力的研究。
