Radionuclide Production with PET Cyclotrons, Applications and Preclinical Experiments

Abstract: Nuclear medicine is based on the radiotracer principle of George de Hevesy and the magic bullet concept by Ehrlich and focuses on the diagnosis, the treatment of diseases and the investigation of normal states within the human body using radiopharmaceuticals. A radiopharmaceutical is an atom or a chemical compound in which one or several atoms are replaced with a radionuclide. Several diagnostic and therapeutic radionuclides like 111In, 99mTc and 131I originate from nuclear reactors via a generator or direct production. But to produce many of the conventional PET radionuclides like 11C, 18F, 13N, 15O a particle accelerator like a cyclotron is necessary. Today there is a rapid increase of the research based on intact monoclonal antibodies (mAbs), engineered mAb fragments and nontraditional antibody-like scaffolds. Approved mAbs and their engineered molecules are now entering the pre-clinical and clinical platforms and both areas have opened up a need for new un-conventional radionuclides with suitable physical and chemical properties that can match all the required half-lives and decay properties set by the different molecules. With the growing interest for imaging and therapeutic nuclear medicine the demand for more and different cyclotron produced radionuclides has increased. This is verified by the increased number of cyclotrons operating in the world. In 2005, ~350 cyclotrons were estimated to be operating in those countries monitored by the International Atomic Energy Agency. A later investigation in 2014 concluded that there are currently more than 950 PET cyclotrons operating in the world. To access a broad variation of radionuclides the accelerator itself should be equipped with different target systems. The overall objective with the work described in this thesis was to increase and extend the medical radionuclide production with special focus in the design of water and solid targets for a MC 17 Scanditronix PET cyclotron. This thesis is based on the development of two targets with two applications and two preclinical experiments related to these targets.