Identification and characterization of the 177Hafnium-containing decay products of 177Lu-AMBA (AMBA = DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2)

380 Objectives: In this study we investigated the fate of the 177Hafnium (177Hf) that forms upon decay of 177Lu-AMBA, a peptide-derivatized DO3A complex that is being studied for the radiotherapeutic treatment of tumors that express the GRP receptor. Methods: HPLC-purified 177Lu-AMBA (621.6 MBq) in stabilizing buffer was stored for 43 days at -20°C. During this time two new nonradioactive peaks formed that we postulated might be isomers of Hf-AMBA. They were isolated and interconversion studies performed using HPLC. Synthesis of a Hf-AMBA standard was attempted by reaction of HfCl4 with AMBA in various solvents. The Hf-AMBA products formed in DMF were purified by HPLC, characterized (elemental analysis, NMR, MS) and coinjected with the products from 177Lu-AMBA decay. Results: In two HPLC methods, the two Lu-AMBA decay products coeluted with a standard of Hf-AMBA made by heating AMBA with HfCl4 in DMF; Hf-AMBA did not form in H20. Analysis results (CHNF) for the Hf-AMBA standard were consistent with its formulation as Hf(IV)AMBA.3TFA.6H2O. The two peaks formed underwent slow interconversion when isolated. By LC/MS, both had a molecular weight (m/z) consistent with formulation as Hf-AMBA. The Hf-AMBA 1H and 13C NMR spectra had chemical shifts similar to those of Lu-AMBA. The ability to obtain an NMR indicated that the Hf is diamagnetic, consistent with Hf(IV), not Hf(III). Conclusions: To our knowledge, the fate of hafnium that forms on decay of 177Lu while the Lu is complexed to a chelator has not been reported. As a result of this study, we conclude that when 177Lu in 177Lu-AMBA undergoes β- decay in H20, the resulting 177Hf is retained in the DO3A-acetyl chelator, but oxidizes from Hf(III) to Hf(IV), forming a stable pair of interconverting isomers.