Radiochemistry and Targetry

Background

Radiochemistry with short-lived PET-radionuclides has a history at Turku extending to middle 1970, at the MGC 20 cyclotron installed in 1974. Various 11C-, 13N-, 15O- 68Ga- , 64Cu- and 18F-labelled tracers have been synthesised for both scientific as well as clinical applications. With the installation in 1992 of the IBA 3D cyclotron at TUCH all work on 15O has been carried out on that machine. Later the installations of the CC18/9 and ACSI TR-19 cyclotrons have allowed further expansion and diversification of our activities

Two strong foci can be discerned from the past work.

  • PET-radiochemistry starts in the radionuclide production target. Research with radionuclide production and targetry with the aim of understanding in-target processes, i.e. ”hot-atom” chemistry and targetry. From this follows production of high quality labelling precursors for PET-radiochemistry.
  • PET is a tracer method only if substances are synthesised in tracer amounts. Synthesis of high specific radioactivity 11C and 18F tracers, development of methods and application for production of said tracers.

During the course of this research the following issues have been central

  • Development of automation for both radionuclide production as well as for radiotracer synthesis. This is mandatory; as radioactivity amounts can be very high and even more importantly, the complexity of the labelling procedures make them very susceptible to errors of human operators.
  • Preclinical evaluation of the radiotracers. The tracers are studied in various in vivoex vivoand in vitro biological models, in order to determine their suitability as PET tracers. This work is carried out as soon as the tracer is available from radiochemistry. This helps us to direct radiosynthetic development on modification on lead molecules. Tracers of lesser interest can also be halted in the radiosynthetic development process, and efforts directed to others. The successful candidates are then further evaluated and eventually taken into use in clinical projects.

Present

At present our activities are based mainly in the facilities located in the PET-building (acronym RK 2), which was taken into use in early 2006. The facilities include the ACSI TR-19 cyclotron (K=19, variable energy, proton beam, beam current 2 x 120 microamperes) and the CC 18/9 cyclotron (k=18, proton and deuteron beams, max proton beam intensity 100 microamperes), as well as radiopharmaceutical laboratories with six hot-cells in clean room environment and four hot-cells for radiochemistry research and development. The radiochemical labs also house all equipment required for analysis of radiotracers and GMP/GLP-tasks. The IBA 3D (K=3.5, deuteron beam, beam current 50 microamperes) cyclotron as well as a separate laboratory with hot-cell for 15O-chemistry is also situated at the PET-building as is two hot cells for 68Ga chemistry, one for preclinical work and one for human studies (GMP)

In the Gadolinia radiochemistry laboratory, six hot-cells are available for radiotracer production and pre-clinical research. These hot-cells are equipped with various automated synthesis devices for 11C-methylation as well as 18F nucleophilic, electrophilic and fluoromethylation devices. Adequate analytical instrumentation is also available. The MGC-20 cyclotron (k=21, multiparticle, max proton beam intensity 10 microamperes), the Gadolinia ”hot-laboratory”, provides this laboratory with the required radio-isotopes. Furthermore the MediCity Preclinical imaging laboratory is available for evaluation and studies of radiotracers.

Education in radiochemistry on an academic level started in 2004 at the University of Turku with establishment of a Chair in Radiochemistry.

Research aims

To efficiently make use of the increased capabilities in radionuclide production and radiosynthesis.

  • To develop radionuclide production with the aim of producing large quantities of 11C-, 13N-, 15O-, 68Ga- 18F-labelled precursors with high specific radioactivity. Also 64Cu is developed.
  • To develop methods and automation for synthesis of high specific radioactivity PET radiotracers.
  • To develop PET radiotracers for studies in humans in both health and disease.

Research strategy

The first research aim includes development of improved cyclotron target technology for the reliable production of 11C, 18F and 64Cu in various chemical forms with a view to increasing production yields, specific activity, chemical purity, improving the economics of production and the availability of the radiotracers. This international cooperation together with the technologies we have earlier developed and will further develop for this, make this approach a viable route to realize the strategic aim.

The second aim will to a large part be realized through our own research efforts, together with scientific collaboration with academic groups worldwide.

The third aim will advantageously be carried out in collaboration with pharma industry. The synthesis of cold precursors for labelling synthesis, reference standards etc. is outside the capabilities of our organization. We therefore actively seek collaboration with outside organizations, prioritizing common projects with a high scientific interest in line with our overall research strategy.