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Neurosciences: Basic ScienceImaging Markers of Neuropathology |
1 Radiopharmaceutical Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, New South Wales, Australia; 2 Neurosciences Research Unit, Australian National University, Canberra, Australian Capital Territory, Australia
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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.
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