3AcFNP-59 for Positron Emission Tomography Imaging of Cholesterol Trafficking and Utilization.

Cholesteryl ester analogues of [F]FNP-59 have the ability to provide information on cholesterol trafficking and utilization at earlier time points than those of [F]FNP-59 or [I]NP-59. It is well-known that free cholesterol and cholesteryl esters have differing distribution profiles and that they can be interconverted enzymatically. Substitution of the ester influences the rate of cholesterol ester hydrolysis and the subsequent mixing of cholesterol esters with the lipid pool in the body.

Automated Radiosynthesis of [F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.

Background: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy.

Room-Temperature Photochemical Copper-Mediated Fluorination of Aryl Iodides.

This report describes a method for the photochemical Cu-mediated fluorination of aryl iodides with AgF via putative aryl radical (Ar•) intermediates. It involves irradiating an aryl iodide with UVB light (λ = 313 nm) in the presence of a mixture of Cu and Cu salts and AgF. Under these conditions, fluorination proceeds at room temperature for substrates containing diverse substituents, including alkoxy and alkyl groups, ketones, esters, sulfonate esters, sulfonamides, and protected amines.

Improved Radiosynthesis and Automation of [C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor.

A new automated radiosynthesis of [C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [C]K2 using a commercial synthesis module.

Classics in Neuroimaging: Untangling the Role of Tau in Neurodegenerative Disorders Using Positron Emission Tomography.

Imaging of misfolded proteins implicated in neurodegenerative disorders using positron emission tomography (PET) imaging has revolutionized dementia research. In this viewpoint, the development of radiotracers for tau PET is highlighted. We draw attention to key innovations that were essential to development of radiotracers for imaging tau, from early imaging agents, through the structure-activity relationship (SAR) studies required to minimize off-target binding of the newer probes in use today.

Stereochemical investigation of conjugate additions of carbon- and heteronucleophiles to ring-substituted nitrosocyclohexenes.

Intermolecular Michael-type conjugate additions of some in situ-generated ring-substituted nitrosocyclohexenes with both carbon- and heteronucleophiles have been found to be highly stereoselective, leading predominantly (or exclusively) to products resulting from axial attack on a half-chair conformation of the nitrosoalkene substrate.

Investigation of the stereochemistry of intermolecular conjugate additions of nucleophiles to acyclic nitrosoalkenes.

Michael-type conjugate additions of γ-chiral aldehyde-derived acyclic nitrosoalkenes have been explored using a series of carbon and hetero nucleophiles. In all cases examined, these reactions are stereoselective, leading exclusively to the anti products.

An expedient reductive method for conversion of ketoximes to the corresponding carbonyl compounds.

A wide array of readily prepared pivalates of ketoximes can be converted to the corresponding ketones in good yields by treatment with iron powder in THF containing catalytic amounts of both trimethylsilyl chloride and glacial acetic acid at room temperature for 30 minutes, followed by a brief aqueous workup.

Efficient methodology for alkylation of vinylnitroso compounds with carbon nucleophiles.

A diverse array of nitrosoalkenes derived from both acyclic and cyclic ketones, as well as aldehydes, via the Denmark protocol using alpha-chloro-O-TBS-oximes can be trapped efficiently in situ by a wide variety of potassium ester enolates to afford conjugate addition products in good yields.