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

Area of Science:

• Nuclear medicine
• Radiochemistry
• Analytical chemistry

Background:

• Peptide Receptor Radionuclide Therapy (PRRT) utilizes Lutetium-177 ((177)Lu) labeled peptides.
• (177)Lu requires high specific activity (SA) for optimal therapeutic efficacy.
• Vendor-provided SA values for (177)Lu may be inaccurate due to target 'burn-up' during production.

Purpose of the Study:

• To develop and validate an alternative method for accurately determining the specific activity of (177)Lu.
• To compare experimentally determined SA values with vendor-stated values.

Main Methods:

• Development of an HPLC-based method involving metal titration of DOTA-peptide with (177)Lu and natural lutetium ((nat)Lu).
• Quantification of (177+nat)Lu content by analyzing the ratio of radiometal-DOTA-peptide to DOTA-peptide after HPLC separation.
• Calculation of precise (177)Lu SA based on experimental data.

Main Results:

• Experimentally determined SA values for (177)Lu were consistently higher than vendor estimates, exceeding them by an average of 27 ± 16% (range 6-73%).
• The developed HPLC method demonstrated high reproducibility, with deviations <2% for samples from the same Lu batch (n ≥ 10).

Conclusions:

• The actual specific activity of (177)Lu is often higher than vendor-reported values.
• Accurate SA determination allows for potentially increased SA of (177)Lu-DOTA-TATE and other Lu-DOTA-peptides used in PRRT.