Nuclear medicine

In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers; which in turn could be accessible by the development of simple, reliable; and efficient radiolabeling procedures. Therefore a further requirement is a cGMP production of imaging probes in automated synthesis modules.

PET/CT and PET/MRI gain

Herein; a novel protocol for the efficient preparation of 18F-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl) iodonium salts without the need of evaporation steps is describe. Labeled aromatics are prepare in high radiochemical yields simply by heating of iodonium [18F]fluorides with the Cu-mediator in methanolic DMF. The iodonium [18F]fluorides are prepare by direct elution of 18F from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF.

The practicality of the novel method is confirm by the racemization-free production of radiolabel fluorophenylalanines, including hitherto unknows 3-[18F]FPhe; in 22–69% isolated radiochemical yields as well as its direct implementation into a remote-control synthesis unit. Widespre implementation of molecular imaging techniques; especially positron emission tomography (PET); and related hybrid methods like PET/CT and PET/MRI in clinical practice have significantly contribute to a considerable increase of diagnostic accuracy in recent years. PET offers the unique opportunity to visualize physiological and pathological processes on the molecular level.

Implementation of molecular imaging

This imaging modality utilizes probes labeled with positron emitting radionuclides (PET-tracers); interacting specifically with molecular targets or biochemical processes of interest. Biodistribution of such probes  determine by the detection of antiparallel γ-photons originating from electron–positron annihilation. PET probes are use for accurate diagnosis and staging of diseases as well as monitoring of therapy success ;(e.g., for tumors, neurological or cardiac disorders). In addition to clinical applications, PET is a powerful tool in drug development which provides fast and precise assessment of pharmacological properties of drug candidates in vivo.

The main challenge of PET-chemistry is the short half-life of the majority of commonly use PET radionuclides like 11C (20.4 min); 13N (10 min) and 15O (2 min) which severely limits the scope of reactions which use for radiolabeling. 18F is the most widely use PET radionuclide owing to the accessibility of no-carrier-add (n.c.a.) 18F in multi-Curie amounts at low and medium energy cyclotrons from [18O]H2O via the high-yielding 18O(p,n)18F nuclear reaction. 18F has a longer half-life (109.8 min) ;which enables extended PET acquisition protocols and shipping of radiofluorinat tracers to remote PET centers as well as favorable decay characteristics like a high positron branching ratio of 97% and a low positron energy (Eβmax 0.63 MeV).

The majority of commonly

The latter enables imaging with high spatial resolution. The vast majority of 18F-labeled PET radiotracers are produce by SN2 and SNAr radiofluorination reactions. In order to be apply for these reactions 18F produced from [18O]H2O has to be transformed into anhydrous [18F]F with high nucleophilicity. Because conventionally; in order to separate the bulk of [18O]water; 18F is trapped on an anion exchange resin. It is recovered using an aqueous solution of suitable bases like K2CO3, Cs2CO3 or tetraalkylammonium hydrogen carbonates. [18O]H2O is then removed by repeatedly time-consuming azeotropic drying with MeCN.