GMP compliant radiosynthesis of11C and18F-labeled PET radiopharmaceuticals with a modular disposable cassette system

Autor: Hessels-Scheper, J.G., Maarsingh, P., Kwizera, C., Zijlma, R., Maas, B., De Vries, A.M.T., Antunes, I.F., Lub-de Hooge, M.N., Boersma, H.H., Dierckx, R.A.J.O., De Vries, E.F.J., Luurtsema, G., Elsinga, P.H.
Přispěvatelé: Molecular Neuroscience and Ageing Research (MOLAR), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Vascular Ageing Programme (VAP)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: European Journal of Nuclear Medicine and Molecular Imaging, 41, 426-427. SPRINGER
ISSN: 1619-7070
Popis: Background Many nuclear medicine departments have an extensive radiopharmaceutical portfolio. Consequently, these multiple PET radiopharmaceuticals have to be produced with the same synthesis module. An important consideration in GMP-compliant PET production is to avoid potential cross-contamination. Flexible cassette-based synthesis modules with disposable components could provide an attractive solution to overcome this hurdle. Because only disposable materials are used, validation of cleaning procedures is not required and maintenance of the system can be reduced. For this purpose, we aimed to develop cassette-based synthesis methods for a variety of11C and18F labeled PET radiopharmaceuticals. Methods In our study, the production processes for the radiosynthesis of [11C]choline, [11C]methionine, [11C]PK11195, [18F]CP18, [18F]FDHT and [18F]FES were implemented on the cassette-based Eckert & Ziegler PharmTracer synthesis module. In order to achieve this goal, there is a need for each tracer to develop a dedicated design of its corresponding cassette. The radiopharmaceuticals were validated according to GMP guidelines and compliance to the required pharmaceutical criteria was tested including novel UPLC analytical QC methods. Results Radiochemical yields obtained with the cassette based system were comparable to literature; [11C]choline 28-52%; [11C]methionine 24-39%; [11C]PK11195 9-15%, [18F]CP18 7-13%, [18F]FDHT 5-10%, [18F]FES 16-28%. Synthesis time was 25 min for [11C]choline and [11C]methionine, 55 min for [11C]PK11195 and 2 h for the 18Flabeled radiopharmaceuticals. All radiopharmaceuticals meets the requirements for specific activities and were >95% pure, isotonic, and complied to the prospective specification for endotoxins, sterility and organic solvents. Discussion and conclusion Multistep synthesis procedures for PET radiopharmaceuticals, involving11C-methylation,11F-fluorination, click chemistry, distillation and solid phase extraction, are feasible with the used cassette-based synthesis module. In addition, purification with HPLC and formulation of the radiopharmaceuticals were successfully performed. The design of the cassettes and the synthesis programs of individual radiopharmaceuticals can easily be adapted for the production of other radiopharmaceuticals, which makes the system very flexible. All cassettes and other materials are disposable; therefore no cross-contamination is possible between the productions of different radiopharmaceuticals. In conclusion, our results show that a variety of11C and11F-radiopharmaceuticals can be reliably produced under GMP-compliant conditions using a common synthesis module with disposable cassettes.
Databáze: OpenAIRE
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