Alternative method to determine Specific Activity of (177)Lu by HPLC

Curr Radiopharm. 2015;8(2):119-22. doi: 10.2174/1874471008666150312162340.

Abstract

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

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Lutetium / chemistry*
  • Octreotide / analogs & derivatives
  • Octreotide / chemistry
  • Organometallic Compounds / chemistry
  • Peptides / chemistry
  • Radiochemistry / methods
  • Radioisotopes / chemistry*
  • Receptors, Peptide / chemistry

Substances

  • Heterocyclic Compounds, 1-Ring
  • Organometallic Compounds
  • Peptides
  • Radioisotopes
  • Receptors, Peptide
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Lutetium
  • lutetium Lu 177 dotatate
  • Octreotide