Fully automated [18F]fluorocholine synthesis in the TracerLab MX FDG Coincidence synthesizer.

INTRODUCTION: We developed a new fully automated method for the radiosynthesis of [18F]fluorocholine by modifying the commercial 2-[18F]fluoro-2-d-deoxy-glucose ([18F]FDG) synthesizer module (GE TracerLab MX, formerly Coincidence). METHODS: [18F]Flurocholine was synthesized by (18)F-fluoroalkylation of N,N-dimethylaminoethanol using [18F]fluorobromomethane as fluoromethylating agent. [18F]Fluorobromomethane was produced by reaction of dibromomethane with [18F]fluoride, assisted by Kryptofix 2.2.2. RESULTS: After purification on solid-phase extraction cartridges, the [18F]fluorocholine was obtained in 15-25% radiochemical yields (decay not corrected), with more than 99% radiochemical purity. Specific activity was more than 37 GBq/micromol. Synthesis time was less than 35 min. CONCLUSION: This new automated synthesis technique provides high and reproducible yields that could be dedicated for routine use with the same [18F]FDG disposable cassette system.

Synthesis and carbon-11 labeling of (R)- and (S)-thionisoxetine, norepinephrine reuptake inhibitors, potential radioligands for positron emission tomography.

Standards and des-methyl precursors of (R)- and (S)-thionisoxetine, potent and selective norepinephrine reuptake inhibitors, were synthesized and radiolabeled with carbon-11. Both enantiomers of the N-methyl-3-(2-thiomethylphenoxy)-3-phenylpropanamine and the 3-(2-thiomethylphenoxy)-3-phenylpropylamine were obtained via multi-step syntheses, while the radiosyntheses were carried out using [11C]CH3I. The radiochemical yields were 26%, decay corrected and the specific radioactivity ranging from 2 to 3 Ci/micromol. The HPLC analyses were performed using a chiral column: during the radiolabeling, no racemization occurred and the isomers were synthesized with high enantiomeric purity.

Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors.

The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with 11C (t1/2=20.4 min, beta+=99.8%) starting from the corresponding des-methyl precursor (14) using [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/micromol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [11C]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [11C]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo.