Automated synthesis and quality control of [68Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging
Abstract Background [68Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [68Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. Results 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97°Celsius, 4 minutes. The mean 3 Good Manufacturing Practice (GMP)-conditions synthesis time was 24 min 27 s (+/- 8 s), and the mean radiolabeling efficiency was 86.96% (Standard deviation (SD) 6.67%). Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.09% (SD 0.25%) assessed by Instant Thin Layer Chromatography and 99.82% (SD 0.092%) assessed by High Pressure Liquid Chromatography. Average 68-germanium breakthrough was 0.0000148%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 hours at room temperature (no augmentation of the [68Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5.00 EU/mL, and the pH was 6.5 (same for the three syntheses). Conclusion The [68Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
ResearchSquare.com - (2023) vom: 16. Okt. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
DANIEL, Thomas [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-2364212/v1 |
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| PPN (Katalog-ID): |
XRA038241722 |
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| 520 | |a Abstract Background [68Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [68Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. Results 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97°Celsius, 4 minutes. The mean 3 Good Manufacturing Practice (GMP)-conditions synthesis time was 24 min 27 s (+/- 8 s), and the mean radiolabeling efficiency was 86.96% (Standard deviation (SD) 6.67%). Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.09% (SD 0.25%) assessed by Instant Thin Layer Chromatography and 99.82% (SD 0.092%) assessed by High Pressure Liquid Chromatography. Average 68-germanium breakthrough was 0.0000148%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 hours at room temperature (no augmentation of the [68Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5.00 EU/mL, and the pH was 6.5 (same for the three syntheses). Conclusion The [68Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings. | ||
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