Browsing by Author "Quinlivan, M"

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    Decreased vesicular acetylcholine transporter and α4β2 nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning
    (Elsevier, 2007-03-26) Quinlivan, M; Chalon, S; Vergote, J; Henderson, J; Katsifis, A; Kassiou, M; Guilloteau, D
    Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with 123IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of 123I, the same animals had in vitro autoradiography performed with 125I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in 123IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in 125I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with 123IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with 125I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging. © 2006 Elsevier Ireland Ltd.
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    Evaluation of [I-123]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation
    (Springer, 2011-08-01) Mattner, F; Bandin, DL; Staykova, M; Berghofer, PJ; Grégoire, MC; Ballantyne, P; Quinlivan, M; Fordham, S; Pham, TQ; Willenborg, DO; Katsifis, A
    The purpose of this study was to assess the feasibility and sensitivity of the high-affinity translocator protein (TSPO) ligand [123I]-CLINDE in imaging TSPO changes in vivo and characterise and compare astroglial and TSPO changes in the cuprizone model of demyelination and remyelination in C57BL/6 mice. Methods C57BL/6 mice were fed with cuprizone for 4 weeks to induce demyelination followed by 2–4 weeks of standard diet (remyelination). Groups of mice were followed by in vivo single photon emission computed tomography (SPECT)/CT imaging using [123I]-CLINDE and uptake correlated with biodistribution, autoradiography, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR). Results The uptake of [123I]-CLINDE in the brain as measured by SPECT imaging over the course of treatment reflects the extent of the physiological response, with significant increases observed during demyelination followed by a decrease in uptake during remyelination. This was confirmed by autoradiography and biodistribution studies. A positive correlation between TSPO expression and astrogliosis was found and both activated astrocytes and microglial cells expressed TSPO. [123I]-CLINDE uptake reflects astrogliosis in brain structures such as corpus callosum, caudate putamen, medium septum and olfactory tubercle as confirmed by both in vitro and in vivo results. Conclusion The dynamics in the cuprizone-induced astroglial and TSPO changes, observed by SPECT imaging, were confirmed by immunofluorescence, RT-PCR and autoradiography. The highly specific TSPO radioiodinated ligand CLINDE can be used as an in vivo marker for early detection and monitoring of a variety of neuropathological conditions using noninvasive brain imaging techniques. © 2011, Springer.
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    Evaluation of the PBR ligand [123I]CLINDE in an animal model of experimental autoimmune encephalomyelitis
    (Australasian Quaternary Association, 2008-05-01) Mattner, F; Linares, D; Staykova, M; Grégoire, MC; Pham, TQ; Bourdier, T; Quinlivan, M; Callaghan, PD; Willenborg, DO; Katsifis, A
    Objectives: The aim of this study was to evaluate the Peripheral Benzodiazepine Receptor (PBR) radioligand [123I]CLINDE in the rat inflammatory disease model of Experimental Autoimmune Encephalomyelitis (EAE). Methods: EAE was induced with blast cells collected from spleen and lymph nodes of Lewis rats induced with myelin basic protein and complete Freund's adjuvant. Biodistribution with [123I]CLINDE was undertaken on EAE rats exhibiting different disease severity and compared to controls.The relationship between inflammatory lesions and tracer uptake was investigated using ex vivo autoradiography and immunohistochemistry. Results: Disease severity was confirmed by histopathology in spinal cord. Results indicate enhanced uptake of [123I]CLINDE in all animals induced with EAE compared to controls. This uptake reflected the ascending nature of the inflammatory lesions ie. uptake in the lumbar spinal cord > thoracic cord > cervical cord > medulla > cerebellum. Uptake of [123I]CLINDE in the lumbar and thoracic cord correlated with disease severity. A 2 and 3 fold enhancement in PBR expression was observed in the brain and spinal cord of animals with a clinical score of 3 compared to controls. Regional [123I]CLINDE uptake closely correlated with localisation of PBR, shown using autoradiography and immunohistochemisty. Conclusions: These results demonstrate the ability of [123I]CLINDE to measure in vivo changes of PBR density according to area of involvement and the severity of disease suggesting it as a potential SPECT tracer for the study of inflammation and multiple sclerosis. © 2022 Journal of Nuclear Medicine
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    PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy
    (Springer-Velag, 2012-11-08) Dedeurwaerdere, S; Callaghan, PD; Pham, TQ; Rahardjo, GL; Amhaoul, H; Berghofer, PJ; Quinlivan, M; Mattner, F; Loc'h, C; Katsifis, A; Grégoire, MC
    Background Recently, inflammatory cascades have been suggested as a target for epilepsy therapy. Positron emission tomography (PET) imaging offers the unique possibility to evaluate brain inflammation longitudinally in a non-invasive translational manner. This study investigated brain inflammation during early epileptogenesis in the post-kainic acid-induced status epilepticus (KASE) model with post-mortem histology and in vivo with [18F]-PBR111 PET. Methods Status epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while controls (N = 9) received saline. Translocator protein (TSPO) expression and microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [18F]-PBR111 volume of distribution (V t) in volume of interests (VOIs) was quantified by means of kinetic modelling and a VOI/metabolite-corrected plasma activity ratio. Results Animals with substantial SE showed huge overexpression of TSPO in vitro in relevant brain regions such as the hippocampus and amygdala (P < 0.001), while animals with mild symptoms displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO expression was associated with OX-42 signal but without obvious cell loss. Similar in vivo [18F]-PBR111 increases in V t and the simplified ratio were found in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01). Conclusion Both post-mortem and in vivo methods substantiate that the brain regions important in seizure generation display significant brain inflammation during epileptogenesis in the KASE model. This work enables future longitudinal investigation of the role of brain inflammation during epileptogenesis and evaluation of anti-inflammatory treatments. © 2012, Springer.
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    Radiosynthesis, in vivo biological evaluation, and imaging of brain lesions with [123I]-CLINME, a new SPECT tracer for the translocator protein
    (Hindawi Publishing Corporation, 2015-06-25) Mattner, F; Quinlivan, M; Greguric, I; Pham, TQ; Liu, X; Jackson, TW; Berghofer, PJ; Fookes, CJR; Dikic, B; Grégoire, MC; Dollé, F; Katsifis, A
    The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT. © 2015 F. Mattner et al.