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Radionuclide Production with PET Cyclotrons, Applications and Preclinical Experiments

Siikanen, Jonathan LU (2015)
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... (More)
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. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Nuklearmedicin bygger på användning av radioaktiva spårämnen, enligt principen av George de Hevesy, för kartläggning av global och regional funktion hos organ eller patologisk vävnad. Nuklearmedicin inkluderar även användningen av ”Magic bullet”-konceptet enligt Ehrlich där en molekyl används som bärare av radionuklider för att få en radiobiologisk terepeutisk effekt på målvävnanden den riktas mot. Nuklearmedicinska metoder fokuserar på diagnostik och behandling av sjukdomar samt utredningen av normaltillstånd i kroppen med hjälp av radioaktiva läkemedel. Ett radioaktivt läkemedel är en atom eller en molekyl, i vilken en eller

flera atomer har ersatts med en radionuklid. Många... (More)
Popular Abstract in Swedish

Nuklearmedicin bygger på användning av radioaktiva spårämnen, enligt principen av George de Hevesy, för kartläggning av global och regional funktion hos organ eller patologisk vävnad. Nuklearmedicin inkluderar även användningen av ”Magic bullet”-konceptet enligt Ehrlich där en molekyl används som bärare av radionuklider för att få en radiobiologisk terepeutisk effekt på målvävnanden den riktas mot. Nuklearmedicinska metoder fokuserar på diagnostik och behandling av sjukdomar samt utredningen av normaltillstånd i kroppen med hjälp av radioaktiva läkemedel. Ett radioaktivt läkemedel är en atom eller en molekyl, i vilken en eller

flera atomer har ersatts med en radionuklid. Många diagnostiska och terapeutiska radionuklider så som 111In, 99mTc och 131I produceras i kärnreaktorer och tillhandahålles via en generator eller en direkt produktion. Men för att kunna producera många av de konventionella positron-emitterande (PET) radionukliderna som till exempel 11C, 18F, 13N, 15O behövs någon form av partikelacclerator där en vanlig sådan för medicinsk tillverkning är av typen cyklotron. Idag sker det en kraftig ökning av forskning baserad på intakta antikropppar (mAb) men även på modifierade mAb-fragment vilket har öppnat upp ett behov av nya icke-konventionella radionuklider med nya krav på fysikaliska och kemiska egenskaper. Med det växande intresset för diagnostisk och terapeutisk nuklearmedicin ökar även efterfrågan på fler och olika cyklotronproducerade radionuklider. Detta verifieras av det ökade antalet cyklotroner verksamma i världen. År 2005 uppskattades cirka 350 cyklotroner vara verksamma i de länder som övervakas av Internationella Atomenergiorganet IAEA. En senare undersökning år 2014 visade att det för närvarande finns mer än 950 cyklotroner för medicinsk produktion. För att kunna producera olika radionuklider måste cyklotronerna utrustas med olika strålmålsystem där själva radionuklidproduktionen sker. Det övergripande målet med arbetet som beskrivs i denna avhandling är att öka och utvidga den medicinska radionuklidproduktionen med särskild inriktning mot utformningen av vatten och fasta strålmål för en MC 17 Scanditronix PET-cyklotron. Denna avhandling är baserad på utvecklingen av två nya strålmål med två applikationer och två prekliniska experiment associerade till dessa strålmål. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor emeritus Lundqvist, Hans, Uppsala University, Medical Radiation Physics, Uppsala, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Radionuclide production, Solid target, Water target, Cyclotron, PET, SPECT, 18F, 89Zr
pages
149 pages
publisher
Medical Radiation Physics, Lund University
defense location
Föreläsningssalen nya strålbehandlingshuset
defense date
2015-05-13 09:00:00
ISBN
978-91-7623-302-3
language
English
LU publication?
yes
id
f7382879-bcc5-41e3-89fb-540f101294b7 (old id 5276328)
date added to LUP
2016-04-04 11:11:00
date last changed
2018-11-21 21:03:11
@phdthesis{f7382879-bcc5-41e3-89fb-540f101294b7,
  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.}},
  author       = {{Siikanen, Jonathan}},
  isbn         = {{978-91-7623-302-3}},
  keywords     = {{Radionuclide production; Solid target; Water target; Cyclotron; PET; SPECT; 18F; 89Zr}},
  language     = {{eng}},
  publisher    = {{Medical Radiation Physics, Lund University}},
  school       = {{Lund University}},
  title        = {{Radionuclide Production with PET Cyclotrons, Applications and Preclinical Experiments}},
  url          = {{https://lup.lub.lu.se/search/files/5713658/5276362.pdf}},
  year         = {{2015}},
}