This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide ¹¹C.

Two methods for the synthesis of ¹¹C-labelled acrylamides have been explored. First, [1-¹¹C]-acrylic acid was obtained from a palladium(0)-mediated ¹¹C-carboxylation of acetylene with [¹¹C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl-¹¹C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [¹¹C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method.

The vinyl halide method was used to synthesize a library of ¹¹C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies.

The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrβ inhibitors that were ¹¹C-labelled at the urea position in 38-78% dc rcy.

The angiotensin II AT₁ receptor antagonist eprosartan was ¹¹C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer.

Three angiotensin II AT₂ ligands were ¹¹C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ distribution and animal PET. The compound was metabolized fast and excreted via urine. High radioactivity was also found in the liver, meaning that more metabolically stable compounds are desirable for future development.