Browsing by Author "Willenborg, DO"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    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.
  • No Thumbnail Available
    Item
    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