RESUMO
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 °C, 4 min. The mean synthesis time of the 3 validation runs under good manufacturing practice (GMP) was 24 min 27 s (± 8 s), and the mean radiochemical yield was 87.0% [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 99.1% (SD 0.25%) assessed by instant thin layer chromatography and 99.8% (SD 0.092%) assessed by high pressure liquid chromatography. average [68Ge] breakthrough was 1.48 × 10-5%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 h 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 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.
RESUMO
BACKGROUND: More than 25% of 99mTc colloidal rhenium sulphide preparations have been reported to have a radiochemical purity of <95% in 11 radiopharmacies. OBJECTIVES: To identify the key parameters involved in radiochemical purity, different preparation procedures were analysed to develop an optimised preparation method. METHODS: In the first part of this study, various data such as the Nanocis kit batch number, the eluate volume, the time between the two final elutions, the temperature and duration of heating were collected and analysed to determine the critical parameters that significantly decrease radiochemical purity. In the second part, a new procedure was applied and then the same parameters and radiochemical purity values were collected and compared with the results before the new procedure. RESULTS: Among 184 preparations, 137 (75%) had a radiochemical purity exceeding 95%, 25 (13.6%) were between 90 and 95% pure and 22 (12%) were below 90%. Significantly higher radiochemical purity was observed after the implementation of the new preparation procedure (89.5% of 374 preparations had radiochemical purities of > 95%). This new procedure consists in lowering the 99mTc eluate volume and time of heating. CONCLUSIONS: The implementation of a new method for the preparation of (99m)Tc colloidal rhenium sulphide based on a comparison of practices in various radiopharmacies resulted in: i) a determination of the critical points of this preparation, ii) an optimised labelling technique to harmonise different practices, and iii) a significant improvement in the preparations radiochemical purity and the quality of the lymphoscintigraphy in the location of sentinel node.