Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K-i = 11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon.

Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [C-11]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [C-11]cyanide with the

bromo precursor. Positron Selleckchem IPI-549 emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility

of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [C-11-cyano]letrozole fraction in arterial plasma were also measured.

Results: [C-11-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 +/- 2.21 Ci/mu mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high Metabolism inhibitor uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84.

Conclusion: [C-11-cyano]Letrozole ID-8 is readily synthesized via a palladium-catalyzed coupling reaction with [C-11]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics

in the brain and peripheral organs. (c) 2009 Elsevier Inc. All rights reserved.”
“Objective: Carotid endarterectomy (CEA) remains the procedure of choice for treatment of patients with severe carotid artery stenosis. The role of carotid artery stenting (CAS) in this patient group is still being defined. Prior single and multicenter studies have demonstrated economic savings associated with CEA compared with CAS. The purpose of this stud), was to compare surgical outcomes and resource utilization associated with these two procedures at the national level in 2005, the first year in which a specific ICD-9 procedure code for CAS was available.

Methods: All patient discharges for carotid revascularization for the year 2005 were identified in the Nationwide Inpatient Sample based on ICD9-CM procedure codes for CEA (38.12) and CAS (00.63).