Isolation of a 177Hf Complex Formed by β-Decay of a 177Lu-Labeled Radiotherapeutic Compound and NMR Structural Elucidation of the Ligand and its Lu and Hf Complexes

Lu-177-AMBA (AMBA = DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2) is being developed for the radio-therapeutic treatment of tumors that express the gastrin-releasing peptide receptor (GRP-R). In this study we investigated the fate of the (177)hafnium (Hf-177) that forms upon the decay of Lu-177 while the latter is complexed with AMBA. When decayed solutions of Lu-177-AMBA were analyzed, it was found that Hf-177 is retained in the DO3A monoamide chelator, forming a pair of interconverting isomers. We report the synthesis and full characterization of Lu-nat-AMBA and the studies performed to demonstrate its correspondence to radioactive Lu-177-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)-NH2] peptide targeting group was found.