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% of 177Lu 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.