Maintaining radiochemical purity of 177Lu-DOTA-PSMA-617 for PRRT

Objectives: Prostate-specific membrane antigen (PSMA) is worldwide increasingly being used in both diagnostics (PET imaging) and therapy. ¹⁷⁷Lu-DOTA-PSMA-617 is very promising as a therapeutic agent for the treatment of prostate cancer. However, successful targeting begins with ensuring a high radiochemical purity (RCP, %) of the therapeutic agent. In this study we aim to maintain RCP (>95%) of therapeutic amounts of ¹⁷⁷Lu-DOTA-PSMA-617 by preventing radiolysis. Quenchers such as gentisic acid, ascorbic acid, methionin and ethanol were added, either separately or in combination, in various concentrations. Moreover, the radiochemical stability was monitored over a longer period of time (>24 hrs).

Methods: Labelling of DOTA-PSMA-617 (ABX, Germany) with ¹⁷⁷LuCl₃ (IDB Holland, the Netherlands) was based on clinical therapeutic amounts (typically 100 µg/ 4 GBq per patient). Here a downscaled validated model was used: 2 µg/80 MBq in 140 µL (de Blois et al, 2014) containing a variety of quenchers and quencher concentrations. Therapeutic amounts were also tested in presence of quenchers or quencher combinations showing most promising results in down-scaled experiments. Radiolabeling was performed by heating at 80^oC for 20 minutes. Incorporation was determined and RCP was monitored in time using radio-HPLC. The radio-HPLC system consists of a Waters Alliance HPLC (the Netherlands) containing a Symmetry C₁₈ column (5 µm, 4.6 mm x 250 mm) and an Osprey radio measurement set-up (Canberra, Belgium).

Results: Measurement on RCP showed that the absence of quenchers was detrimental for the stability of the product. Without any quenchers added the RCP decreased 2.9% per hour. Within 2 hours after labeling the RCP decreased below clinical release criteria of 95% and decreased to approximately 24 % in 24 hours. Addition of ascorbic acid (3.5 mM), methionin (3.5 mM) or a mix consisting of gentisic acid, ascorbic acid and ethanol (3.5 mM, 3.5 mM and 7% respectively) reduced the decrease in RCP to approximately 5% within the first 5 hours and approximately 72% within 24 hrs after labeling. Addition of ethanol (10%) or methionine (10 mM) reduced the decrease in RCP to approximately 5% in 24 hours. RCP measurements on therapeutic amounts showed similar results.

Conclusion: The RCP of ¹⁷⁷Lu-DOTA-PSMA-617 decreased rapidly over time in absence of quenchers. The addition of quenchers e.g. methionine and ethanol, during or after labeling, reduced effects of radiolysis and thus maintained RCP for at least 24 hours on both down scaled and therapeutic amounts. Research Support: None