Cagnolini Aldo, D'Amelio Nicola, Metcalfe Edmund, Nguyen Hanh D, Aime Silvio, Swenson Rolf E, Linder Karen E
Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, New Jersey 08540, USA.
Inorg Chem. 2009 Apr 6;48(7):3114-24. doi: 10.1021/ic802328a.
(177)Lu-AMBA (AMBA = DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)) is being developed for the radiotherapeutic treatment of tumors that express the gastrin-releasing peptide receptor (GRP-R). In this study we investigated the fate of the (177)hafnium ((177)Hf) that forms upon the decay of (177)Lu while the latter is complexed with AMBA. When decayed solutions of (177)Lu-AMBA were analyzed, it was found that (177)Hf is retained in the DO3A monoamide chelator, forming a pair of interconverting isomers. We report the synthesis and full characterization of (nat)Lu-AMBA and the studies performed to demonstrate its correspondence to radioactive (177)Lu-AMBA. We also report the synthesis and characterization of Hf-AMBA and, by NMR studies, show structural analogies between Hf-AMBA, its parent compound Lu-AMBA, and the unmetallated AMBA ligand. In the NMR spectra of both the metallated and unmetallated AMBA ligand, a stacking interaction between the amino benzoyl residue in the linker and a tryptophan in the truncated bombesin [BBN(7-14)-NH(2)] peptide targeting group was found.
（177）镥-AMBA（AMBA = DO3A-CH(2)CO-G-[4-氨基苯甲酰基]-QWAVGHLM-NH(2)）正被开发用于对表达胃泌素释放肽受体（GRP-R）的肿瘤进行放射治疗。在本研究中，我们研究了（177）镥（（177）Hf）在与AMBA络合时衰变所形成的（177）铪的去向。当分析（177）镥-AMBA的衰变溶液时，发现（177）铪保留在DO3A单酰胺螯合剂中，形成一对相互转化的异构体。我们报告了天然镥（nat）-AMBA的合成及全面表征，以及为证明其与放射性（177）镥-AMBA的一致性而进行的研究。我们还报告了铪-AMBA的合成与表征，并通过核磁共振研究表明铪-AMBA、其母体化合物镥-AMBA和未金属化的AMBA配体之间的结构相似性。在金属化和未金属化的AMBA配体的核磁共振谱中，发现连接体中的氨基苯甲酰基残基与截短的蛙皮素[BBN(7 - 14)-NH(2)]肽靶向基团中的色氨酸之间存在堆积相互作用。
