Application click chemistry for PET

PhD ceremony: Ms. L. Mirfeizi, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Application click chemistry for PET

Promotor(s): prof. P.H. Elsinga, prof. B.L. Feringa, prof. R.A.J.O. Dierckx

Faculty: Medical Sciences

In this thesis, the preparation of several receptor binding ligands via 1,3-dipolar cycloaddition of azide and alkynes , also called a click reaction for [18F]-radiolabeling of Positron Emission Tomography (PET) is described. The work meets the challenges in radiochemistry that are focused on: short synthesis time, very small amount of reagent, easy and reliable synthesis, versatility of the labelling method. Superimposed on these challenges is the stringent requirement that the products be consistently pure and that the results be reproducible as ultimately the protocols may be used to prepare compounds for injection in patients. The copper-catalyzed 1,3-dipolar cycloaddition of alkynes and azides (CuAAC) and the copper-free cycloaddition promoted by ring strain have proven to be both reliable and orthogonal ligation methods. The CuAAC reaction meets the challenges mentioned above such as being fast; it can be applied under a wide range of conditions, and is selective. In a field where simple and fast reactions are crucial, it is only normal that “click” chemistry emerged as an excellent radiolabeling technique. Throughout this thesis, two main goals were pursued: The first is to develop click chemistry methodology for the synthesis of PET tracers with focus on 18F as radionuclide and the second part was to apply click chemistry for the synthesis and evaluation of biologically active molecules. In conclusion click chemistry is a highly valuable approach for biomedical application. One of the unique and important properties of click chemistry is its bio-orthogonal character.