Three types of metabolic control of oxidative metabolism are observed in the various tissues that have been studied by phosphorous magnetic resonance spectroscopy. The principal control of oxidative metabolism in skeletal muscle is by ADP (or P1/phosphocreatine). This
Reactive oxygen species
(ROS) are believed to play a major role in the proinflammatory, M1-polarized
form of neuroinflammation. However, it has been difficult to assess
the role of ROS and their role in neuroinflammation in animal models
of disease because of the absence of probes capable of measuring their
presence with the functional imaging technique positron emission tomography
(PET). This study describes the synthesis and in vivo evaluation of
[18F]ROStrace, a radiotracer for imaging superoxide in
vivo with PET, in an LPS model of neuroinflammation. [18F]ROStrace was found to rapidly cross the blood–brain barrier
(BBB) and was trapped in the brain of LPS-treated animals but not
the control group. [18F]ox-ROStrace, the
oxidized form of [18F]ROStrace, did not cross the BBB.
These data suggest that [18F]ROStrace is a suitable radiotracer
for imaging superoxide levels in the central nervous system with PET.
The fibrillary aggregation of the protein alpha synuclein (Asyn) is a hallmark of Parkinson's disease, and the identification of small molecule binding sites on fibrils is essential to the development of diagnostic imaging probes. A series of molecular modeling, photoaffinity labeling, mass spectrometry, and radioligand binding studies were conducted on Asyn fibrils. The results of these studies revealed the presence of three different binding sites within fibrillar Asyn capable of binding small molecules with moderate to high affinity. A knowledge of the amino acid residues in these binding sites will be important in the design of high affinity probes capable of imaging fibrillary species of Asyn.
The copper-catalyzed H-F insertion into α-diazocarbonyl compounds is described using potassium fluoride (KF) and hexafluoroisopropanol. Access to complex α-fluorocarbonyl derivatives is achieved under mild conditions, and the method is readily adapted to radiofluorination with [(18)F]KF. This late-stage strategy provides an attractive route to (18)F-labeled biomolecules.
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