Alternative Method to Determine Specific Activity of Lu-177 by HPLC

Peptide Receptor Radionuclide Therapy (PRRT) with Lu-177-DOTA-peptides requires Lu-177 with high specific activity (SA) and values >740 GBq Lu-177 per mg Lu to maximise the atom% of Lu-177 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 Lu-177 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 (Lu-177), and a unknown amount of metal (Lu177+nat). Based on an HPLC separation of radiometal-DOTA-peptide and DOTA-peptide, and the concordant ratio of these components the metal content (Lu177+nat) can be calculated, and eventually the SA of Lu-177 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 Lu-177 is apparently often higher as stated by vendors in comparison to the experimentally determined actual values. For this reason, the SA of Lu-177-DOTA-TATE and other Lu-DOTA-peptides could be increased accordingly.