title: Isolation of a 177Hf complex formed by beta-decay of a 177Lu-labeled radiotherapeutic compound and NMR structural elucidation of the ligand and its Lu and Hf complexes.
abstract: (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.
authors.affiliation: Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, New Jersey 08540, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Cagnolini
authors.forename: Nicola
authors.initials: N
authors.lastname: D'Amelio
authors.forename: Edmund
authors.initials: E
authors.lastname: Metcalfe
authors.forename: Hanh D
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Swenson
authors.forename: Karen E
authors.initials: KE
authors.lastname: Linder
mesh_terms: D018360:Crystallography, X-Ray; D006195:Hafnium / Q000737:chemistry*; D007554:Isotopes / Q000737:chemistry; D008024:Ligands; D008187:Lutetium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D007554:Isotopes; D008024:Ligands; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D008187:Lutetium; D006195:Hafnium