Specific binding of [<sup>18</sup>F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain

Maschauer, Simone; Haller, Adelina; Riss, Patrick J.; Kuwert, Torsten; Prante, Olaf; Cumming, Paul

doi:10.1111/jnc.13370

Cited by 15 publications

(19 citation statements)

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“…Published values for the specific activity of 18 F-labeled PET imaging probes using carrier free 18 F-fluoride are generally in the range of 50–500 GBq/µmol [2,43]. Fluorine-18 labeled radioligands developed for the central nervous system exhibiting specific activities ranging from 11–135 GBq/µmol were successful in addressing the dopamine transporter and the monoamine-oxidase-A in PET studies with rats [44,45]. The established radiotracer [ 11 C]PHNO for human PET imaging of the less abundantly expressed dopamine D3 receptor has been applied in studies with specific activities of 31–67 GBq/µmol [26,46].…”

Section: Discussionmentioning

confidence: 99%

“…In the past, no successful PET study selectively visualizing the D3 receptor has been reported in rodents. A study conducted to characterize the in vivo pharmacokinetics and pharmacological properties of [ 11 C]PHNO at the D3 receptor in rats used an intracerebral beta-sensitive system [45]. Shortly thereafter, PET studies using [ 11 C]PHNO were reported in cats and humans [60,61].…”

Section: Discussionmentioning

confidence: 99%

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In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

et al. 2016

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Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4) with the candidate [ 18 F]2b offering a B max of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [ 18 F]2a and [ 18 F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

et al. 2016

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“…The saturation binding parameters B max and K D can be estimated separately from serial PET studies entailing a range of ligand specific activities, as in a rat PET study with the MAO-A ligand [ 18 F]-fluoroethylharmine. 92 However, this fully quantitative approach is technically very demanding, and an initial attempt for the case of [ 11 C]-( R )-PK11195 failed due to the low specific binding in brain of living pigs. 85 The simplest form of quantitation for routine PET studies consists of scaling the regional uptake at some time-window after tracer administration to the total injected dose (standard uptake value: SUV).…”

Section: Approaches To Pet Quantitationmentioning

confidence: 99%

Sifting through the surfeit of neuroinflammation tracers

Cumming

Burgher

Patkar

et al. 2017

J Cereb Blood Flow Metab

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The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [C]-( R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) (TSPO). Investigations by positron emission tomography (PET) revealed microgliosis in numerous brain diseases, despite the rather low specific binding signal imparted by [C]-( R)-PK11195. There has since been enormous expansion of the repertoire of TSPO tracers, many with higher specific binding, albeit complicated by allelic dependence of the affinity. However, the specificity of TSPO PET for revealing microglial activation not been fully established, and it has been difficult to judge the relative merits of the competing tracers and analysis methods with respect to their sensitivity for detecting microglial activation. We therefore present a systematic comparison of 13 TSPO PET and single photon computed tomography (SPECT) tracers belonging to five structural classes, each of which has been investigated by compartmental analysis in healthy human brain relative to a metabolite-corrected arterial input. We emphasize the need to establish the non-displaceable binding component for each ligand and conclude with five recommendations for a standard approach to define the cellular distribution of TSPO signals, and to characterize the properties of candidate TSPO tracers.

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“…PET/MRI scanning. All rats in the sucrose diet (n = 9) and normal diet (n = 9) groups were scanned using [ 18 F]DPA714 at (baseline; 6 weeks old) just prior to the binge sucrose protocol, and again (follow-up) after 12 weeks of the sucrose intake protocol, when they were 18 weeks old (Fig. 1a).…”

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A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity

Patkar

Mohamed

Narayanan

et al. 2021

Sci Rep

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While the dire cardiometabolic consequences of the hypercaloric modern ‘Western’ diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [18F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months. Compared to a control group fed with normal chow (n=9), the sucrose rats indeed showed widespread increases in the availability of cerebral binding sites for the microglial marker, despite normal weight gain compared to the control diet group. Subsequent immunofluorescence staining of the brains confirmed the PET findings, showing a widespread 20% increase in the abundance of IBA-1-positive microglia with characteristic ‘semi-activated’ morphology in the binge sucrose rats, which had 23% lower density of microglial endpoints and 25% lower mean process length compared to microglia in the control rats with ordinary feeding. GFAP immunofluorescence showed no difference in astroglial coverage in the sucrose rats, except for a slight reduction in hypothalamus. The binge sucrose diet-induced neuroinflammation was associated with a significant elevation of white blood cell counts. Taking these results together, we find that long-term intake of sucrose in a binge paradigm, similar in sucrose content to the contemporary Western diet, triggered a low-grade systemic and central inflammation in non-obese rats. The molecular mechanism of this phenomenon remains to be established.

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Specific binding of [¹⁸F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain

Cited by 15 publications

References 40 publications

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

Sifting through the surfeit of neuroinflammation tracers

A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity

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Specific binding of [18F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain

Cited by 15 publications

References 40 publications

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

Sifting through the surfeit of neuroinflammation tracers

A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity

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Product

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Specific binding of [¹⁸F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain