A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-fluoroethyl)-L-tyrosine.

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18)F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18)F]-fluoride ion. Three model linker-vector molecules 7a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy.

Exploration of the structure-activity relationship of the diaryl anilide class of ligands for translocator protein--potential novel positron emitting tomography imaging agents.

A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.

[¹⁸F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO).

A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated.

Synthesis of the positron-emitting radiotracer [(18)F]-2-fluoro-2-deoxy-D-glucose from resin-bound perfluoroalkylsulfonates.

A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [(19/18)F]-) is described, which employs supported perfluoroalkylsulfonate precursors , where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [(19)F]fluoride ion afforded protected FDG [(19)F]- as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [(19)F]- was shown to produce [(19)F]FDG.