Development and validation of the HPLC method for quality control of radiolabelled DOTA-TATE and DOTA-TOC preparations

Radzik, Marcin; Pijarowska-Kruszyna, Justyna; Jaroń, Antoni; Maurin, Michał; Decristoforo, Clemens; Mikołajczak, Renata; Garnuszek, Piotr

doi:10.1016/j.nucmedbio.2020.11.005

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Many studies have already been published on the validation of analytical methods applied to radiopharmacy, in particular on the assessment of the radiochemical purity of specific radiopharmaceuticals. However, to date, none of these studies have combined an evaluation by HPLC and TLC [ 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

et al. 2022

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Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68Ga/177Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177Lu-PSMA-1.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

et al. 2022

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“…When analysing routine batches several peaks could be detected in UV, the earliest corresponding in retention time with PSMA I&T, another major peak at the retention time of nat Lu-PSMA I&T, other peaks were smaller and could not be identi ed, but can be explained being complexes of PSMA I&T with other metals. For quanti cation of the total amount of PSMA I&T, the sum of the peaks was used for calculation, assuming no relevant differences in absorption of the metal complexes, which has been shown for DOTATATE (25). In the radiochromatograms of routine samples, several radioactive impurities could be separated, with two peaks eluting after the main peak.…”

Section: Discussionmentioning

confidence: 99%

Improved Quality Control of [177Lu]Lu-PSMA I&T

Kraihammer

Garnuszek

Bauman

et al. 2023

Preprint

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Background: Targeted radionuclide therapy with [177Lu]Lu-PSMA I&T (Zadavotide guraxetan) has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide. Several methods to determine the radiochemical purity have been reported but also limitations in the HPLC analysis due to retention of the sample and tailing effects when using standard gradients containing trifluoroacetic acid (TFA). We here report on the validation of a method for quality control of [177Lu]Lu-PSMA I&T including determination of radiochemical purity, identity testing and limit test for PSMA I&T by HPLC using a Phosphate buffer /Acetonitrile gradient system, complemented with a TLC system with 0.1N Citrate buffer pH5 as mobile phase including validation of the methods, batch and stability data as well as identification of the main radiochemical impurity by mass spectrometry. Results: The described HPLC method met the defined acceptance criteria in terms of accuracy, specificity, robustness, linearity, range and LOQ. HPLC analysis revealed symmetrical peaks and quantitative recovery from the column. Batch data showed a radiochemical purity >95% as determined by HPLC, stability data a pronounced degradation due to radiolysis, which could be limited by addition of ascorbic acid, dilution and storage at low temperatures. The main radiochemical impurity was found to be the de-iodinated form of [177Lu]Lu-PSMA I&T. TLC analysis allowed to determine the amount of free Lu-177 even in the presence of DTPA in the final formulation. Conclusion: Overall the described combination of HPLC and TLC provides a reliable tool for quality control of [177Lu]Lu-PSMA I&T.

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Radionuclide generators

Pijarowska-Kruszyna

Pocięgiel

Mikołajczak

2022

Nuclear Medicine and Molecular Imaging

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Development and validation of the HPLC method for quality control of radiolabelled DOTA-TATE and DOTA-TOC preparations

Cited by 5 publications

References 27 publications

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

Improved Quality Control of [177Lu]Lu-PSMA I&T

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Development and validation of the HPLC method for quality control of radiolabelled DOTA-TATE and DOTA-TOC preparations

Cited by 5 publications

References 27 publications

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1

Improved Quality Control of [177Lu]Lu-PSMA I&amp;T

Radionuclide generators

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Improved Quality Control of [177Lu]Lu-PSMA I&T