Desarrollo de procedimientos automatizados de síntesis de radiofármacos PET marcados con carbono-11 a temperatura ambiente y purificación mediante extracción en fase sólida
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Química nuclear
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QUINCOCES FERNÁNDEZ, Gemma. “Desarrollo de procedimientos automatizados de síntesis de radiofármacos PET marcados con carbono-11 a temperatura ambiente y purificación mediante extracción en fase sólida”. Peñuelas Sánchez, Iván (dir.). Tesis doctoral. Universidad de Navarra, Pamplona, 2015
The continued increase in the number of PET studies with carbon-11 labelled radiopharmaceuticals, along with the limitations in space and laboratory equipment is a real problem and a radiation protection challenge. Adaptation of synthesis procedures to solid-phase supported approaches implies a global simplification of the synthesis system, an increase in safety and a substantial decrease in the overall necessary time to carry out the synthesis. Objectives The aims of this study were: (1) to design, assemble and test a fully-automated solid-phase supported synthesis system based on commercial modules for the simultaneous production of L-[Methyl-(11C)]Methionine (MET) and [11C]-Choline (CHOL); (2) set-up such system also for the routine production of [11C]-(+)-á- dihydrotetrabenazine (DTBZ); and (3) design and test a solid phase extraction based simplified system using whole-sterile single use "plug & play" kits for synthesis of MET and CHOL using Eckert&Ziegler Modular Lab modules. Methodology A commercial Tracerlab FXc module (GE) was modified to carry out the simultaneous production of MET and CHOL starting from [11C]methyl iodide. A completely automated synthesis sequence was programmed and 48 synthesis runs made to demonstrate performance of the system. Reaction times, synthesis yields and full QC of both radiopharmaceuticals were carried out. Such system was further adapted (including control interface and running sequences) for the synthesis of DTBZ using two Alumina N cartridges for final purification of the product and 54 synthesis runs carried out. Solvents were then evaporated under vacuum with helium flow. Finally, for the "plug and play" approach kits were set-up in a LFC using single-use sterile medical material, sterilised and further used for the synthesis of MET and CHOL using the designed Modular Lab based synthesis system. A control interface and a synthesis sequence programs were also designed for such purpose. Results and conclusions Simultaneous production of MET and CHOL was finalised in just six minutes with mean productions of 2.4 and 2.7 GBq respectively, and radiopharmaceutical purity according to pharmacopoeia standards. [11C]DTBZ (1.94 ±0.13 GBq) was obtained with radiochemical purity >99% while residual solvents were below PhEur stablished levels. The ¿plug &play¿ system produced MET and CHOL with radiopharmaceutical purity with 5.0 and 5.3 GBq mean production yields. The new procedures minimises the time required for the preparation of the system, avoids cleaning runs, facilitates fulfilment of GMP quality standards and improves radiation protection to personnel.

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