We synthesized C-11 labeled alpha(7) nAChR ligands, (R)-2-[C-11]methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([C-11](R)-MeQAA) and its isomer (S)-[C-11]MeQAA, for in vivo investigation with positron emission tomography (PET). Then, the potential of (R)- and (S)-[C-11] MeQAA for in vivo imaging of alpha(7) nAChR in the brain was evaluated in mice and monkeys.
Methods: The binding affinity for alpha(7) nAChR was measured using rat brain. Biodistribution and in vivo receptor blocking
studies were undertaken buy GSK2118436 in mice. Dynamic PET scans were performed in conscious monkeys.
Results: The affinity for alpha(7) nAChR was 41 and 182 nM for (R)- and (S)-MeQAA, respectively. The initial uptake in the mouse brain was high ([C-11](R)-MeQAA: 7.68 and [C-11](S)-MeQAA: 6.65 %dose/g at 5 min). The clearance of [C-11](R)-MeQAA was slow in the hippocampus (alpha(7) nAChR-rich region) but was rapid in the cerebellum (alpha(7) nAChR-poor region). On the other hand, the clearance was fast for [C-11](S)-MeQAA in all regions. The brain uptake of [C-11](R)-MeQAA was decreased by methyllycaconitine (alpha(7) nAChR antagonist) treatment. In monkeys, alpha(7) nAChRs
were highly distributed in the thalamus and cortex but poorly distributed Elafibranor datasheet in the cerebellum. The high accumulation was observed in the cortex and thalamus for [C-11](R)-MeQAA, while the uptake was rather homogeneous for [C-11](S)-MeQAA.
Conclusions: [C-11](R)-MeQAA was successfully synthesized and showed high uptake to the brain. However, since the in vivo selectivity for alpha(7) nAChR was not enough, further PET kinetic analysis or structure optimization is needed for specific visualization of brain alpha(7) nAChRs in vivo. (C) 2010 Elsevier Inc. All rights reserved.”
“This study describes
a colorimetric method for detecting and genotyping Foretinib solubility dmso hepatitis C virus (HCV) in which four different oligonucleotide probes are fixed onto microwell plates and hybridized separately with biotinylated PCR amplification products derived from clinical samples. The first probe capable of hybridizing with all seven known HCV genotypes was used for overall detection, and the remaining probes were used to recognize specifically genotypes 1-3. When combined with an improved silica-based RNA extraction method, the sensitivity of the test was 50 IU/mL Eighty-five of the 86 samples analyzed (98.8%) yielded results in agreement with reference detection methods. The remaining sample was HCV-RNA positive in the COBAS Amplicor qualitative assay, but was negative using the reverse-hybridization method. The usefulness of the new genotyping test was confirmed by comparison with direct sequencing of PCR products: 98% of samples tested (54/55) were in agreement using the two methods (21, 7 and 27 from genotypes 1-3, respectively). The single discrepancy might have been due to a mixed HCV infection.