Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride.

An improved, automated synthesis of [(18)F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064+/-3076 MBq of [(18)F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both >or= 95%. Specific activity was ca. 50 GBq/micromol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [(18)F]FDOPA.

Efficient radiosynthesis of carbon-11 labelled uncharged Thioflavin T derivatives using [11C]methyl triflate for beta-amyloid imaging in Alzheimer's Disease with PET.

The synthesis of carbon-11 amino function labelled uncharged Thioflavin T derivatives is known to be performed by reaction of the demethyl-precursors with [11C]methyl iodide but the labelling yields are only mediocre. The use of [11C]methyl triflate improved the radiochemical yield of three potential beta-amyloid imaging PET-radiotracers significantly. Performance of the labelling reaction by reacting the corresponding precursor molecules with [11C]methyl triflate for 1 min at 80 degrees C led to radiochemical yields of 44+/-10% (n=5) for [11C]6-Me-BTA-1, 68+/-4% (n=10) for [11C]BTA-1 and 58+/-2% (n=5) for [11C]6-OH-BTA-1 with respect to [11C]methyl triflate. In production runs (60 min, 50 microA) up to 6500 MBq (mean: 4000+/-1900 MBq) of [11C]6-Me-BTA-1, 7900 MBq (mean: 6000+/-1000 MBq) of [11C]BTA-1 and 7100 MBq (mean: 6300+/-600 MBq) of [11C]6-OH-BTA-1 could be obtained ready for intravenous injection. The radiochemical purity was >95% with specific activities in the range of 80-120 GBq/micromol (EOS) within a total synthesis time of less than 40 min after EOB.

Molecular characterization of lantibiotic-synthesizing enzyme EpiD reveals a function for bacterial Dfp proteins in coenzyme A biosynthesis.

The lantibiotic-synthesizing flavoprotein EpiD catalyzes the oxidative decarboxylation of peptidylcysteines to peptidyl-aminoenethiols. The sequence motif responsible for flavin coenzyme binding and enzyme activity is conserved in different proteins from all kingdoms of life. Dfp proteins of eubacteria and archaebacteria and salt tolerance proteins of yeasts and plants belong to this new family of flavoproteins. The enzymatic function of all these proteins was not known, but our experiments suggested that they catalyze a similar reaction like EpiD and/or may have similar substrates and are homododecameric flavoproteins. We demonstrate that the N-terminal domain of the Escherichia coli Dfp protein catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'-phosphopantetheine. This reaction is essential for coenzyme A biosynthesis.