Improved quality control of [¹⁷⁷Lu]Lu-PSMA I&T

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Analytical Chemistry

Background:

• [177Lu]Lu-PSMA I&T (zadavotide guraxetan) is an effective targeted radionuclide therapy for advanced prostate cancer.
• Existing radiochemical purity assays for [177Lu]Lu-PSMA I&T face limitations with standard HPLC methods.
• Trifluoroacetic acid (TFA) in HPLC gradients can cause sample retention and peak tailing.

Purpose of the Study:

• To validate a robust HPLC and TLC method for the quality control of [177Lu]Lu-PSMA I&T.
• To ensure accurate determination of radiochemical purity, identity, and impurity levels.
• To identify the primary radiochemical impurity and assess stability.

Main Methods:

• High-Performance Liquid Chromatography (HPLC) using a Phosphate buffer/Acetonitrile gradient.
• Thin-Layer Chromatography (TLC) with 0.1N Citrate buffer (pH 5).
• Mass spectrometry for impurity identification.

Main Results:

• The validated HPLC method demonstrated accuracy, specificity, robustness, linearity, and adequate limit of quantification (LOQ).
• HPLC analysis yielded symmetrical peaks and quantitative recovery, with radiochemical purity consistently exceeding 95%.
• Stability studies revealed degradation due to radiolysis, mitigated by ascorbic acid, dilution, and cold storage; the main impurity was the de-iodinated form.

Conclusions:

• The combined HPLC and TLC method offers a reliable analytical tool for [177Lu]Lu-PSMA I&T quality control.
• This validated method addresses limitations of previous assays, enhancing therapeutic agent reliability.
• The findings support consistent and safe application of [177Lu]Lu-PSMA I&T in clinical settings.