Synthesis and Quality Control of 68Ga-PSMA PET/CT Tracer used in Prostate Cancer Imaging and Comparison with 18F-Fluorocholine as a Reference Point

Szydło, Marcin; Pogoda, Dawid; Kowalski, Tomasz; Pocięgiel, Mateusz; Jadwiński, Michał; Amico, Andrea

doi:10.4172/2380-9477.1000126

Cited by 7 publications

(3 citation statements)

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“…Additional aspects to be considered include accessibility to the radioisotope, production time and procedure, exposure during production, the number of patients that can be attended in the long term, and the effect of the radioisotope on image quality. In this sense, most of these parameters are favored when working with the automatic synthesis module-based production of [ 68 Ga]Ga-PSMA-11—like that presented in this work—which provides further advantages for this product [ 25 ]. Although there are other possibilities for synthesis, such as direct cyclotron production or manual-based production, automatic synthesis module-based production of [ 68 Ga]Ga-PSMA-11 allows very low radiation exposure for technicians, high reproducibility, and compliance with local health regulatory and good manufacturing practice (GMP) standards [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

et al. 2021

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Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP > 98%) and in serum for up to 1 h (RCP > 95%). The lipophilicity was determined as −3.80 ± 0.15, while the serum protein binding (SPB) was <17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of >8.5 and a tumor-to-blood ratio of >3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.

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Section: Introductionmentioning

confidence: 99%

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

et al. 2021

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“…In this context, between 68 Ga-PSMA 11, 68 Ga-PSMA 617 and 68 Ga-PSMA I&T, as the theranostic agents, 68 Ga-PSMA I&T is commonly used for PET/CT-imaging [5,6,7]. Szydlo et al in their study, they described the procedure for labeling PSMA ligands and quality control as a medicinal product, and then compared the results of 68 Ga-PSMA and 18F-fluorocholine [8]. PSMA radiopharmaceuticals labeled gallium-68 can be used to detect prostate cancer (PCa) cells due to excessive expression of PSMA.…”

Section: Introductionmentioning

confidence: 99%

Validation of HPLC method for the determination of chemical and radiochemical purity of a 68Ga-labelled EuK-Sub-kf-(3-iodo-y-) DOTAGA

2021

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The prostate-specific membrane antigen (PSMA) represents an ideal biomarker for molecular imaging. Various PSMA-targeted radioligands are available for prostate cancer imaging. In this study, labelling of PSMA I&T with 68 Ga as well as validation of the radiochemical purity of the synthesis product by reverse phase radio HPLC method are intended. Since the standard procedure for the quality control (QC) was not available, definition of chemical and radiochemical purity of 68 Ga-PSMA I&T was carried out according to Q2 (R1) ICH guideline. The standard QC tests were analyzed with Scintomics 8100 radio-HPLC system equipped with a radioactivity detector. The method was evaluated in terms of linearity, precision and accuracy, LOQ, robustness parameters and specificity. To assess the radiochemical and chemical purity of 68 Ga-2 PSMA I&T, the developed method was validated to apply safely to patients. An excellent linearity was found between 1 μg/mL and 30 μg/mL, with a limit of detection and limit of quantitation of 0.286 μg/mL and 0.866 μg/mL, respectively for 68 Ga-PSMA I&T. The recovery was 96.8 ± 3.8%. The quality control of the final product was performed many times with validated radio-HPLC method found comply with ICH requirements, thus demonstrating the accuracy and robustness of the method for routine clinical practice.

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“…The second method is the use of a vial kit for the preparation of gallium-68 labeled peptides that is currently used at the Department of Nuclear Medicine, University of Pretoria, South Africa. 9 Although literature is available describing both kit vial and automated synthesis methods for [ 68 Ga]Ga-PSMA-11 synthesis in the same facility, [11][12][13][14] to our knowledge, no in-depth discussion of the radiation protection, departmental logistics, and complete outcome of synthesis parameters exists. A recent investigation by Meisenheimer et al only compared manual labeling (not kit-based labeling) and automated synthesis based on reliability and reproducibility without taking into account additional important considerations like radiation exposure or pharmaceutical quality of the final product.…”

Section: Introductionmentioning

confidence: 99%

Production of [⁶⁸Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach

Kleynhans

Rubow

et al. 2020

Labelled Comp Radiopharmac

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The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Coldkits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ 68 Ga] Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [ 68 Ga]Ga-PSMA-11 were analyzed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analyzed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labeling (25-40 μSv). The exposure during kit-based labeling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals.

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Synthesis and Quality Control of 68Ga-PSMA PET/CT Tracer used in Prostate Cancer Imaging and Comparison with 18F-Fluorocholine as a Reference Point

Cited by 7 publications

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Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Validation of HPLC method for the determination of chemical and radiochemical purity of a 68Ga-labelled EuK-Sub-kf-(3-iodo-y-) DOTAGA

Production of [⁶⁸Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach

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Synthesis and Quality Control of 68Ga-PSMA PET/CT Tracer used in Prostate Cancer Imaging and Comparison with 18F-Fluorocholine as a Reference Point

Cited by 7 publications

References 0 publications

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Validation of HPLC method for the determination of chemical and radiochemical purity of a 68Ga-labelled EuK-Sub-kf-(3-iodo-y-) DOTAGA

Production of [68Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach

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Production of [⁶⁸Ga]Ga‐PSMA: Comparing a manual kit‐based method with a module‐based automated synthesis approach