In the current study, N-C-11-methylated compound of NCFB, [C-11]Me-NCFB was synthesized and evaluated
for the visualization of BACE1 in brain.
Methods: BACE1 inhibitory constant was measured by FRET assay. [C-11]Me-NCFB was synthesized from NCFB with [C-11]methyl triflate. To Selisistat cost evaluate properties of [C-11]Me-NCFB, log P value, stability in mouse plasma and brain uptake index were measured. The biodistribution in 6-week-old ddY mice was also studied.
Results: BACE1 inhibitory constant showed an affinity of Me-NCFB to the enzyme (IC50 = 2.3 +/- 0.80 mu M). [C-11]Me-NCFB was synthesized in a 3.0% +/- 0.55% decay-corrected radiochemical yield. [C-11]Me-NCFB showed high lipophilicity, high stability in mouse plasma and blood-brain barrier (BBB) permeability. Injected to 6-week-old ddY mice, [C-11]Me-NCFB penetrated BBB and was retained in the brain (0.79% +/- 0.22% ID/g at 2 min and 0.75% +/- 0.08% ID/g at 60 min after injection, respectively), moreover, Selleckchem GSK3326595 rapid blood clearance was observed.
Conclusion: [C-11]Me-NCFB could have a potential as a PET probe for the imaging
of BACE1 in the brain. (C) 2013 Elsevier Inc. All rights reserved.”
“Adult height, a marker of early-life environment, has been sporadically associated with suicide risk. We have examined adult height and attempted suicide risk in a cohort of 1,102,293 Swedish men and, in fully-adjusted analyses, found decreasing stepwise associations between height and attempted suicides by any means and most specific means. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“In the last few years click chemistry reactions, and in particular copper-catalyzed cycloadditions have been used extensively for the preparation of new bioconjugated molecules such as Non-specific serine/threonine protein kinase F-18-radiolabeled radiopharmaceuticals for positron emission tomography (PET). This study is focused on the synthesis of the Siemens imaging biomarker [F-18]RGD-K5. This cyclic peptide contains an amino acid sequence which is a well known binding motif for integrin alpha(v)beta(3) involved
in cellular-adhesion to the extracellular matrix. We developed an improved “”click”" chemistry method using Cu(I)-Monophos as catalyst to conjugate [F-18]fluoropentyne to the RGD-azide precursor yielding [F-18]RGD-K5. A comparison is made with the registered Siemens method with respect to synthesis, purification and quality control. [F-18]RGD-K5 was obtained after 75 min overall synthesis time with an overall radiochemical yield of 35% (EOB). The radiochemical purity was >98% and the specific radioactivity was 100-200 GBq/mu mol at the EOS. (C) 2013 Elsevier Inc. All rights reserved.”
“Qualitative poor decision-making and associated altered neuronal activation patterns have been described for the users of several drugs, amongst others for stimulants like amphetamine and MDMA.