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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cagnolini, A. Articles by Linder, K. PubMed Articles by Cagnolini, A. Articles by Linder, K.

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

¹ Ernst Felder Laboratories, Bracco Research USA, Princeton, New Jersey

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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.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cagnolini, A. Articles by Linder, K. PubMed Articles by Cagnolini, A. Articles by Linder, K.