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Digital archive of theses discussed at the University of Pisa


Thesis etd-03122008-012903

Thesis type
Tesi di dottorato di ricerca
Thesis title
Automation and Quality Assurance in Radiopharmaceutical Production
Academic discipline
Course of study
Relatore Prof.ssa Martini, Claudia
  • FDG
  • PET
  • radiopharmaceutical
Graduation session start date
The use of radiolabelled bioactive molecules and Molecular Imaging (MI) for diagnostic purposes and clinical or preclinical research is gaining importance in the field of medicine and pharmaceutical sciences. PET (Positron Emission Tomography) is an emerging MI modality widely adopted in Nuclear Medicine to detect in vivo biodistribution of positron emitting tracers and relate their fate to diagnostic conclusion; in particular a wide range of applications has been developed for the diagnosis, staging and therapy response of cancer.
18F, with its half-life of approximately 110 minutes, has gained a prominent role among the positron-emitting radionuclides in many imaging studies and diagnostic procedures. This radionuclide needs to be incorporated into bioactive molecules rapidly, efficiently, and in such a way that the 18F-labelled product retains biological activity. These issues may pose different problems ranging from available chemistry routes, to adequate substrates and/or precursors, to the obvious necessity of adopting technical solutions to prevent radiation exposure of personnel involved in the production and risk of radioactive pollution
Computer-controlled automation of the synthetic process of PET radiopharmaceuticals is then strongly desirable, in particular during scale-up of activity and routine operation, when the level of radioactivity is too high to be compatible with direct equipment handling or source manipulation. Automation is also expected to improve process reliability and performance optimization.
Specific expertise and know-how on radiochemistry practice, chemical step automation and on available technologies and methodological approaches have been acquired during this work. They have developed from learning how to handle unsealed positron-emitting sources, produced at the IFC-CNR Cyclotron, to application of basic radiochemistry of short-lived radionuclides and finally to the use, maintenance and exploitation of a full automated processing unit, that is used for the routine production of the radiopharmaceutical 18F-2-fluoro-2-deoxyglucose (FDG). Furthermore, due the fact that such an automated unit is installed in a GMP (Good Manufacturing Practice) licensed site for radiopharmaceutical manufacturing at the IFC CNR all the above has to comply with quality assurance principles in the form of validated procedures and Standard Operative Procedures (SOPs).
The experience with the fully automate unit (TRACERlab FxFDG) has been functional to learn the features that are necessary for any automated component to conform with, official standard for radiopharmaceutical production as well as the strong or weak points of such an approach.
This experience is being transferred to a radiochemistry procedure set up during the earlier period of the doctorate school, and still developed at the PET-Cyclotron and Radiopharmaceutical Chemistry Dept of the Institute of Clinical Phisiology of the CNR in Pisa. This procedure is aimed at converting the manual radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) and its conjugation to a di-Boc-protected insulin to a PC-operated, remote-controlled process.
This part of the project will require further investment allocation and, although still ongoing, it should be considered outside the scope of the present work