GMP-compatible production of Zr-89- N-sucDf-PSMA (Zr-89-DFO)

Ziel/Aim The multistep procedure for labeling the Fe-N-sucDf-PSMA with Zr-89 is time consuming and relatively complicated. The time-consuming removal of iron is difficult to reconcile with Good Manufacturing Practice (GMP). The iron separation should therefore take place before the GMP-relevant labeling process. The question of the study was whether the iron-free precursor can be labelled with zirconium-89 after several months of storage without impairing the yield, cell binding and internalization [1].

Methodik/Methods The iron was removed from Fe-N-sucDf-PSMA by transchelation to EDTA. The isolation of the N-sucDf-PSMA from [Fe(III)EDTA]^- and EDTA was performed by using a Sep-Pak C18 plus light cartridge and a PD MidiTrap G-10 gravity column. The iron-free peptide was stored at 5 ^oC in aqueous solution for several months. The stored compound was labeled with Zr-89 by adjusting the pH 6,8 – 7,2 with 1 M sodium carbonate, 0.5 M HEPES buffer and 0.25 M sodium acetate (5 mg/mL gentisic acid). Yield and radiochmical purity was dtermined by HPLC. The radioligand was characterized in vitro by the calculation of the specific binding and internalization in PSMA positive LNCaP cells at 2 h and 3 h.

Ergebnisse/Results The radiochemical yield of the stored compound was 98.6±1.4% and after purification, the radiochemical purity was≥99.9%. After 3 h incubation, the specific binding of the fresh compound was 13.1±1.6% higher than the stored compound, however, the internalization of the stored compound is 7.8±0.5% higher than the fresh one.

Schlussfolgerungen/Conclusions Chemical reactivity, specific binding and internalization using the iron-free precursor after being stored at 5 ^oC in aqueous solution for a period of 6 months remain unaffected. This result supports the possibility of producing a stock solution of N-sucDf-PSMA. Thus, Zr-89-PSMA DFO can be produced fast and reliable following GMP guidelines using an automatic synthesis module.

 

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• Literatur/References

• 1 Vázquez SM, Endepols H, Fischer T. et al. Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer. Mol Imaging Biol. 2021 Aug 9 doi: 10.1007/s11307-021-01632-x Epub ahead of print. PMID: 34370181

Publication History

Article published online:
14 April 2022