Researchers have validated the analytical methods needed to confirm the radiochemical purity of a zirconium-89 labelled PSMA-targeting compound, [89Zr]Zr-PSMA-I&T, before it can be released to patients. Because no monograph for this radiolabelled compound exists in the European Pharmacopoeia, the team adapted its validation to the ICH Q2(R1) guideline, testing the methods for specificity, accuracy, linearity, robustness, repeatability, intermediate precision, limits of quantification and detection, and range.
The work, published as a research article in EJNMMI Radiopharmacy and Chemistry, addresses a specific clinical problem in prostate cancer follow-up. Prostate cancer is the second most common cancer among men worldwide, after lung cancer. When the disease may have returned after localized treatment, clinicians assess rising prostate-specific antigen (PSA) levels alongside CT scans, bone scintigraphy, gallium-68 or fluorine-18 PSMA PET/CT, and occasionally fluorine-18 FDG PET/CT.
A recurring challenge arises when a patient who has previously received localized treatment shows a rise in PSA above 0.2 ng/ml while PSMA PET/CT imaging shows no corresponding change. The authors attribute this to a weak signal-to-noise ratio or to the minimal size of the suspected tumour. To tackle it, the team developed a zirconium-89 labelling of PSMA-I&T. Zirconium-89’s longer half-life allows late PET/CT imaging, which may provide a better signal-to-noise ratio because uptake of the compound is complete by the time images are acquired.
Before any such radiopharmaceutical can be administered, its radiochemical purity must be measured reliably. The validated techniques were high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC), the two standard analytical platforms used in radiopharmacy quality control.
Both methods effectively separated [89Zr]Zr-PSMA-I&T from zirconium-89 impurities, including [89Zr]ZrCl4, [89Zr]Zr(ox)2 and [89Zr]Zr colloids. Recovery percentages fell within the range of 90 to 110 percent for both HPLC and TLC, meeting the accuracy criterion. Linearity was established over the standard concentration ranges, with a coefficient of determination (R²) exceeding 0.99 for both methods.
The methods also proved robust and precise. The limits of quantification were 0.18 MBq/mL for HPLC and 0.22 MBq/mL for TLC, defining the smallest amounts of the compound the techniques can reliably measure.
Beyond the validation itself, the team carried out a stability study and forced degradation experiments on the product. The stability study showed that the compound remained stable over three days.
The authors conclude that the analytical methods developed in the study comply with the recommendations of the European Association of Nuclear Medicine (EANM) and the European Pharmacopoeia.
Subject of Research: Validation of HPLC and TLC methods for determining the radiochemical purity of the zirconium-89 labelled PSMA-I&T radiotracer for clinical use
Article Title: Validation of analytical methods for determining the radiochemical purity of [89Zr]Zr-PSMA-I&T for clinical use
Article References: Yamout, M., Kane, F., Tonnelet, D., Vera, P., & Bohn, P. (2026). Validation of analytical methods for determining the radiochemical purity of [89Zr]Zr-PSMA-I&T for clinical use. EJNMMI Radiopharmacy and Chemistry. https://doi.org/10.1186/s41181-026-00503-6
Image Credits: AI Generated
DOI: 10.1186/s41181-026-00503-6
Keywords: zirconium-89, PSMA-I&T, radiochemical purity, HPLC, TLC, method validation, ICH Q2(R1), prostate cancer, biochemical recurrence, radiopharmacy, PET/CT, stability study
News Source: Bethany Barker. (October 28, 2026). Validated HPLC and TLC methods confirm purity of zirconium-89 PSMA tracer for clinical use. Scienmag.
