Alternative method to determine specific activity of ¹⁷⁷Lu by HPLC

Peptide Receptor Radionuclide Therapy (PRRT) with ¹⁷⁷Lu-DOTA-peptides requires ¹⁷⁷Lu with high specific activity (SA) and values >740 GBq ¹⁷⁷Lu per mg Lu to maximise the atom% of¹⁷⁷Lu over total Lu. Vendors provide SA values which are based on activity and mass of the target, whereas due to "burn-up" of target, these SA values are not accurate. For a radiochemist the SA of ¹⁷⁷Lu is of interest prior to radiolabeling. An alternative method to determine SA was developed by HPLC, which includes a metal titration of a known amount of DOTA-peptide with a known amount of activity (¹⁷⁷Lu), and a unknown amount of metal (^177+natLu). Based on an HPLC separation of radiometal-DOTA-peptide and DOTA-peptide, and the concordant ratio of these components the metal content (^177+natLu) can be calculated, and eventually the SA of ¹⁷⁷Lu can be accurately determined. These experimentally determined SA values exceeded the estimated values provided by vendors by 27±16%, (range 6-73 %). The deviation of SA values for samples from the same Lu batch was <2% (n≤10). In conclusion: the SA of ¹⁷⁷Lu is apparently often higher as stated by vendors in comparison to the experimentally determined actual values. For this reason, the SA of ¹⁷⁷Lu-DOTA-TATE and other Lu-DOTA-peptides could be increased accordingly.