357166-64-4

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• 64248-63-1 3,5-difluorobenzonitrile 

Relevant academic research and scientific papers

Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

Purpose: Synaptic abnormalities have been implicated in a variety of neuropsychiatric disorders, including epilepsy, Alzheimer’s disease, and schizophrenia. Hence, PET imaging of the synaptic vesicle glycoprotein 2A (SV2A) may be a valuable in vivo biomarker for neurologic and psychiatric diseases. We previously developed [11C]UCB-J, a PET radiotracer with high affinity and selectivity toward SV2A; however, the short radioactive half-life (20 min for 11C) places some limitations on its broader application. Herein, we report the first synthesis of the longer-lived 18F-labeled counterpart (half-life: 110 min), [18F]UCB-J, and its evaluation in nonhuman primates. Methods: [18F]UCB-J was synthesized from the iodonium precursors. PET imaging experiments with [18F]UCB-J were conducted in rhesus monkeys to assess the pharmacokinetic and in vivo binding properties. Arterial samples were taken for analysis of radioactive metabolites and generation of input functions. Regional time–activity curves were analyzed using the one-tissue compartment model to derive regional distribution volumes and binding potentials for comparison with [11C]UCB-J. Results: [18F]UCB-J was prepared in high radiochemical and enantiomeric purity, but low radiochemical yield. Evaluation in nonhuman primates indicated that the radiotracer displayed pharmacokinetic and imaging characteristics similar to those of [11C]UCB-J, with moderate metabolism rate, high brain uptake, fast and reversible binding kinetics, and high specific binding signals. Conclusion: We have accomplished the first synthesis of the novel SV2A radiotracer [18F]UCB-J. [18F]UCB-J is demonstrated to be an excellent imaging agent and may prove to be useful for imaging and quantification of SV2A expression, and synaptic density, in humans.

RADIOLABELED PHARMACEUTICALS AND METHODS OF MAKING AND USING SAME

In one aspect, the invention comprises compounds that bind to the synaptic vesicle protein SV2A and that can be useful as radiotracers for positron emission tomography. In another aspect, the invention comprises methods of imaging the brain, measuring synaptic density or diagnosing neurological diseases such as Alzheimer's disease, psychiatric disorders such as depression, and metabolic disorders such as diabetes comprising detecting the compounds of the invention by positron emission tomography (PET).

Compound having 2-fluorophenyloxymethane structure

There is provided a compound having a good miscibility with another liquid crystal compound and having a combination of a low viscosity (η), high storage stability, and high T?i even after being used to produce a liquid crystal composition. In