A protocol for controlled reactivity shift in the 2,2-difluorovinyl motif used for selective S-F and C-F bond formation.

Positron emission tomography (PET) is a powerful imaging technique for biomedical research, drug development and medical diagnosis. The power of PET lies in biochemically selective radiotracers, labelled with positron emitters like fluorine-18 image chemical processes in vivo. A rapid and remarkably efficient, unprecedented protocol to select between S-F and C-F bond formation based on activation of 1,1-difluoroethylene groups followed by selective oxidation or reduction is described.

Evaluation of a First PET Tracer Suitable for Imaging the Sigma-2 Receptor in the Brain of Nonhuman Primates.

The sigma-2 receptor (σ2R), recently identified as transmembrane protein 97, is expressed in many cell types and mediates important functions in both the peripheral and central nervous systems. Over the years, σ2R has emerged as a potential therapeutic target for cancer and neurological disorders such as Alzheimer's disease (AD). The currently available σ2R radiotracers have been developed primarily for cancer imaging with limited brain uptake.

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis.

Background: CXCR3 is a chemokine receptor and is expressed in innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation.

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis.

CXCR3 is a chemokine receptor and is expressed on innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation.

Preclinical evaluation of new C-11 labeled benzo-1,4-dioxane PET radiotracers for brain α2C adrenergic receptors.

As one of the nine subtypes of adrenergic receptors (ARs) in the brain, α2C-ARs play essential roles in emotion and memory, and are implicated in neuropsychiatric disorders, including depression, Alzheimer's disease, substance use disorder, and schizophrenia. A recently developed α2C-AR specific positron emission tomography (PET) radiotracer, [C]ORM-13070, showed promise for imaging α2C-ARs in the brain. Herein, we prepared highly potent C-11 labeled benzo-1,4-dioxane derivatives and compared them with [C]ORM-13070, aiming to improve the specific binding signal, as evaluated by in vivo rodent brain PET imaging.

PET Imaging Radiotracers of Chemokine Receptors.

Chemokines and chemokine receptors have been recognized as critical signal components that maintain the physiological functions of various cells, particularly the immune cells. The signals of chemokines/chemokine receptors guide various leukocytes to respond to inflammatory reactions and infectious agents. Many chemokine receptors play supportive roles in the differentiation, proliferation, angiogenesis, and metastasis of diverse tumor cells.

PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives.

Epinephrine (E) and norepinephrine (NE) play diverse roles in our body's physiology. In addition to their role in the peripheral nervous system (PNS), E/NE systems including their receptors are critical to the central nervous system (CNS) and to mental health. Various antipsychotics, antidepressants, and psychostimulants exert their influence partially through different subtypes of adrenergic receptors (ARs).

Synthesis, radiosynthesis, and positron emission tomography neuroimaging using 5-[ F]fluoro-L-amino suberate.

System xc- (Sx -) has emerged as a new biological target for PET studies to detect oxidative and excitotoxic stress. Notably, applications have, thus far, been limited to tumour imaging although Sx ) may play a major role in neurodegeneration. The synthesis procedures of tosylate precursor and its translation to Sx - PET tracer 5[18F]fluoro-L-amino suberate by manual and automated radiosyntheses are described.

Influx rate of F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts.

Purpose: F-fluoroaminosuberic acid (F-FASu) is a recently developed amino acid tracer for positron emission tomography (PET) of oxidative stress that may offer improved tumour assessment over the conventional tracer F-fluorodeoxyglucose (F-FDG). Our aim was to evaluate and relate dynamic F-FASu and F-FDG uptake with pharmacokinetic modelling to transporter protein expression levels in a panel of diverse tumour xenograft lines.

Methods: Four different tumour xenograft lines were implanted in female athymic nude mice: MAS98.

Stereospecific radiosynthesis of 3-fluoro amino acids: access to enantiomerically pure radioligands for positron emission tomography.

A variety of substituted non-racemic aziridine-2-carboxylates equivalent to amino acids were prepared and subjected to ring opening reaction by [18F/19F]fluoride. The regio and stereospecific ring opening depends on the substituents on the nitrogen as well as both the carbons of aziridines. The applicability of the methods to afford access to 3-[18F/19F]fluoro amino acids are illustrated.

Poly(ADP-ribose) Polymerase in Neurodegeneration: Radiosynthesis and Radioligand Binding in ARC-SWE tg Mice.

We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution.