Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system

Wilson, Alan A.; Sadovski, Oleg; Nóbrega, José N.; Raymond, Roger; Bambico, Francis Rodriguez; Nashed, Mina G.; García, Armando; Bloomfield, Peter; Houle, Sylvain; Mizrahi, Romina; Tong, Junchao

doi:10.1016/j.nucmedbio.2017.05.011

Cited by 24 publications

(19 citation statements)

References 26 publications

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“…20 A number of radiolabeled analogues of dihydro-methidium (also known as hydromethidine) have been synthesized and evaluated in vitro and in vivo, including [ 3 H]hydromethidine and [ 11 C]hydromethidine. 21,22 [ 3 H]Hydromethidine is oxidized by superoxide and hydroxyl radicals and has been evaluated in animal models of stroke and cisplatin-induced nephrotoxicity. 23,24 A recent paper on the radiosynthesis and preliminary in vivo evaluation of [ 11 C]methidium has also been reported.…”

Section: Discussionmentioning

confidence: 99%

“…23,24 A recent paper on the radiosynthesis and preliminary in vivo evaluation of [ 11 C]methidium has also been reported. 22 It should also be noted that our group reported the in vitro properties of methidium toward various forms of ROS in the patent literature (U.S. Patent 9,035,057) but did not pursue radiolabeling of this compound because of our interest in developing an 18 F-labeled radiotracer for imaging ROS.…”

Section: Discussionmentioning

confidence: 99%

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Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Hou

Hsieh

et al. 2017

ACS Chem. Neurosci.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Hou

Hsieh

et al. 2017

ACS Chem. Neurosci.

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“…Unfortunately, there are only very few reports on PET tracers that could be used to specifically image ROS species in vivo. There are some studies concerned with the development of 18 F‐ and 11 C‐labelled dihydrophenantridine derivatives, which bind in their oxidised form to DNA in cells and become trapped, whereas the nonoxidised form is rapidly cleared from the cells. These studies are promising, because the tracers showed ROS‐specific uptake in vitro and in vivo using an animal model of neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

Radiosynthesis of an ¹⁸F‐fluoroglycosylated aminoferrocene for in‐vivo imaging of reactive oxygen species activity by PET

Toms

Reshetnikov

Maschauer

et al. 2018

Labelled Comp Radiopharmac

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The imaging of reactive oxygen species (ROS) at the molecular level with high sensitivity and specificity by positron emission tomography (PET) could be of enormous interest to increase our knowledge about ROS activity and signalling, especially in tumours. The aim of this research was to optimise the click chemistry‐based radiosynthesis of an 18F‐labelled aminoferrocene glycoconjugate that was derived from an N‐alkylaminoferrocene lead structure known to have anticancer activity in vitro. Applying the solvent system phosphate buffer/THF (12/5), Cu(OAc)2 and sodium ascorbate as reducing agent at 60°C, the alkyne 1 reacted with the 18F‐labelled glycosyl azide [18F]2 in the presence of carrier 3 (47μM) to obtain carrier‐added [18F]4 in a radiochemical yield of 85%. Interestingly, the addition of carrier was essential for sufficient radiochemical yield, because it suppressed the oxidation of no‐carrier‐added (n.c.a.) [18F]4. Future work will include the formulation of c.a. [18F]4 for studying its biodistribution in tumour‐bearing mice.

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“…A number of radiolabeled analogs of dihydromethidium (a.k.a. hydromethidine), which is the corresponding N -methyl analog of DHE, have been synthesized and evaluated in vitro and in vivo [ 56 , 57 ]. [ 3 H]Dihydromethidium is oxidized by both superoxide and hydroxyl radicals and has been evaluated in animal models of stroke and cisplatin-induced nephrotoxicity [ 58 , 59 ].…”

Section: Pet Radiotracers For Imaging Rosmentioning

confidence: 99%

“…[ 3 H]Dihydromethidium is oxidized by both superoxide and hydroxyl radicals and has been evaluated in animal models of stroke and cisplatin-induced nephrotoxicity [ 58 , 59 ]. A recent paper has also reported the radiosynthesis and preliminary in vivo evaluation of [ 11 C]dihydromethidium [ 57 ]. This compound shows high brain uptake in microPET imaging studies, but a detailed analysis of the mechanisms of uptake and trapping of this radiotracer was not conducted.…”

Section: Pet Radiotracers For Imaging Rosmentioning

confidence: 99%

PET Imaging of Microglial Activation—Beyond Targeting TSPO

et al. 2018

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Neuroinflammation, which involves microglial activation, is thought to play a key role in the development and progression of neurodegenerative diseases and other brain pathologies. Positron emission tomography is an ideal imaging technique for studying biochemical processes in vivo, and particularly for studying the living brain. Neuroinflammation has been traditionally studied using radiotracers targeting the translocator protein 18 kDa, but this comes with certain limitations. The current review describes alternative biological targets that have gained interest for the imaging of microglial activation over recent years, such as the cannabinoid receptor type 2, cyclooxygenase-2, the P2X7 receptor and reactive oxygen species, and some promising radiotracers for these targets. Although many advances have been made in the field of neuroinflammation imaging, current radiotracers all target the pro-inflammatory (M1) phenotype of activated microglia, since the number of known biological targets specific for the anti-inflammatory (M2) phenotype that are also suited as a target for radiotracer development is still limited. Next to proceeding the currently available tracers for M1 microglia into the clinic, the development of a suitable radiotracer for M2 microglia would mean a great advance in the field, as this would allow for imaging of the dynamics of microglial activation in different diseases.

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Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system

Cited by 24 publications

References 26 publications

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Radiosynthesis of an ¹⁸F‐fluoroglycosylated aminoferrocene for in‐vivo imaging of reactive oxygen species activity by PET

PET Imaging of Microglial Activation—Beyond Targeting TSPO

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Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system

Cited by 24 publications

References 26 publications

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Development of a Positron Emission Tomography Radiotracer for Imaging Elevated Levels of Superoxide in Neuroinflammation

Radiosynthesis of an 18F‐fluoroglycosylated aminoferrocene for in‐vivo imaging of reactive oxygen species activity by PET

PET Imaging of Microglial Activation—Beyond Targeting TSPO

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Radiosynthesis of an ¹⁸F‐fluoroglycosylated aminoferrocene for in‐vivo imaging of reactive oxygen species activity by PET