Aspects on radiolabeling of 177Lu-DOTA-TATE: After C18 purification re-addition of ascorbic acid is required to maintain radiochemical purity

Abstract

Purpose: Radiolabeled peptides like 177Lu-DOTA-TATE are vulnerable to radiolysis, which results in decreasedradiochemical purity (RCP) of these radiopeptides. Gentisic acid (GA) and ascorbic acid (AA) are well known ingredientsto reduce the effects of radiolysis. Currently, there is a trend to change the procedure from a manual to a cassette-basedautomated labeling and to introduce a C18 solid phase extraction (SPE) post-radiolabeling in order to removenon-incorporated 177Lu from the injection solution. However, with the introduction of SPE purification, GA and AAmight effectively be removed from injection solution with a concordant dramatically drop of the RCP. Therefore weinvestigated the impact of tC18 SPE purification on the RCP of 177Lu-DOTA-TATE.Methods: We compared the manual radiolabeling procedure with the cassette-based automated radiolabeling procedurewith/out tC18 SPE purification cartridge. The effect of tC18 purification on RCP of 177Lu-DOTA-TATE wasinvestigated by HPLC as function of the post-radiolabeling time and the concentration of activity.Results: After tC18 SPE purification, GA and AA were effectively removed and resulted in volume-dependent decreasein RCP, e.g. <95% after 5h in 20 mL. Re-addition of AA directly after tC18 SPE purification resulted in a RCP ≥95% at72h. In addition, with the cassette-based automated radiolabeling procedure we also found 28% of the original activityremaining in the activity-containing vial and tubing vs. < 1% with the manual procedure.Conclusion: Re-addition of AA post tC18 SPE purification is required to maintain RCP of 177Lu-DOTA-TATE.