GMP-consistent automatic synthesis of Lu-177 labelled DOTA-tate and the subsequent influence for stability

Objectives Radio labelled somatostatin analogues, such as 177Lu-DOTA-tate ([177Lu-DOTA0,Tyr3]-Octreotate) play an important role in peptide receptor-targeted radionuclide therapy (PRRT).177Lu-DOTA-tate can be produced either manually or by robotics and C18 columns are recently introduced as a “safety net” post synthesis in order to remove non-incorporated 177Lu. However, 177Lu-DOTA-tate is vulnerable to radiolysis, which results in decreased radiochemical purity (RCP). Gentisic- and ascorbic acid are well known to reduce the effects of radiolysis. With the introduction of this “safety net”, however, gentisic acid and ascorbic acid might be removed, thus RCP might drop dramatically. Therefore we investigated the effect of tC18 purification on RCP of 177Lu-DOTA-tate as a f(t) post labelling vs. control (=without tC18 purification).

Methods The effect of tC18 purification on RCP of 177Lu-DOTA-tate was investigated by HPLC as function of time post radiolabelling vs. control (=without tC18 purification), and concentration of activity in 5 or 20 mL. In addition, the effects on RCP of with vs. without re-addition of ascorbic or gentisic acid was also quantified time-dependently post radiolabelling.

Results After tC18 purification gentisic acid and ascorbic acid were indeed effectively removed from the injectate. RCP with tC18 purification was >95% after 5h in 5 mL, while RCP in 20 mL decreased much more rapidly and resulted in 95% RCP after ~5h and 74% at 24h. RCP of control (=without tC18 purification) was ≥95% at ~ 72h in 5 and in 20 mL. RCP of fractions after re-addition of ascorbic acid was ≥95% at ~ 72h. Re-addition of gentisic acid had no beneficial effect on RCP.

Conclusions RCP of 177Lu-DOTA-tate decreases time- and volume-dependently after tC18 purification in comparison to control. These results clearly demonstrate the necessity for re-addition of ascorbic acid after tC18 purification