Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

Wilson, Alan A.; García, Armando; Parkes, Jun; McCormick, Patrick N.; Stephenson, Karin A.; Houle, Sylvain; Vasdev, Neil

doi:10.1016/j.nucmedbio.2007.12.009

Cited by 182 publications

(176 citation statements)

References 35 publications

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“…Determination of the extent of formation of radioactive metabolites in rat brain extracts and rat plasma was performed as previously described. 16 Briefly, rats (male, Sprague-Dawley, 300 to 350 g) were injected with 50 to 100 MBq of high specific activity […”

Section: Metabolite Studies In Ratmentioning

confidence: 99%

Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Rusjan

Wilson

Miler

et al. 2014

J Cereb Blood Flow Metab

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This article describes the kinetic modeling of [ 11 C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)11 C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90-minute PET scans after an intravenous injection of [ 11 C]SL25.1188. Complementary arterial blood sampling was acquired. Radioactivity was quickly eliminated from plasma with 80% of parent compound remaining at 90 minutes. Metabolites were more polar than the parent compound. Time-activity curves showed high brain uptake, early peak and washout rate consistent with known regional MAO-B concentration. A two-tissue compartment model (2-TCM) provided better fits to the data than a 1-TCM. Measurement of total distribution volume (V T ) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(V T )o8%), low betweensubject variability (B20%), and quick temporal convergence (within 5% of final value at 45 minutes). Logan graphical method produces very good estimation of V T . Regional V T highly correlated with previous postmortem report of MAO-B level (r 2 ¼ X0.9). Specific binding would account from 70% to 90% of V T . Hence, V T measurement of [11 C]SL25.1 1 88 PET is an excellent estimation of MAO-B concentration.

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Section: Metabolite Studies In Ratmentioning

confidence: 99%

Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Rusjan

Wilson

Miler

et al. 2014

J Cereb Blood Flow Metab

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“…Details of [ 18 F]-FEPPA synthesis has been described elsewhere (Wilson et al, 2008). It is reliably and quickly labeled with [ 18 F] by nucleophilic displacement of a tosylate leaving group in a fast one-step reaction, yielding a sterile, pyrogen-free product after purification and formulation.…”

Section: Radiochemistrymentioning

confidence: 99%

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [¹⁸F]-FEPPA

Mizrahi

Rusjan

Kennedy

et al. 2012

J Cereb Blood Flow Metab

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132

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[ 18 F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [ 18 F]-FEPPA total distribution volume in human brains. In addition, [ 18 F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands.

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“…More recent studies in larger samples using the same radioligand, but without blood sampling for full quantification, did not replicate these findings (15)(16)(17). Concerns regarding the low signal-to-noise ratio of (R)-[ 11 C]PK11195 sparked the development of a series of second-generation TSPO radioligands, showing much greater specific binding (18)(19)(20)(21). These tools have subsequently been used to revisit the question of higher levels of TSPO in psychosis (22)(23)(24)(25)(26).…”

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confidence: 99%

Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

Plavén-Sigray

Matheson

Collste

et al. 2018

Biological Psychiatry

110

102

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BACKGROUND: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects. METHODS: PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (V T ), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients' TSPO levels compared with healthy control subjects. RESULTS: Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower V T in patients relative to no difference (all BFs .

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Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

Cited by 182 publications

References 35 publications

Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [¹⁸F]-FEPPA

Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

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Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

Cited by 182 publications

References 35 publications

Kinetic Modeling of the Monoamine Oxidase B Radioligand [11C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Kinetic Modeling of the Monoamine Oxidase B Radioligand [11C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA

Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

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Product

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Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Kinetic Modeling of the Monoamine Oxidase B Radioligand [¹¹C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [¹⁸F]-FEPPA