Abstract for presentation at 38th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine 2008

Synthesis and Evaluation of [123I]CLINDE a Novel Ligand for Imaging of Neurodegeneration and Inflammation Using SPECT

  • Ms Filomena Mattner, Radiopharmaceutical Research Institute, Australia
  • Dr David Linares, Australian National University, Australia
  • Dr Maria Staykova, Australian National University, Australia
  • Ms Patrice Ballantyne, Radiopharmaceutical Research Institute, Australia
  • Ms Paula Berghofer, Radiopharmaceutical Research Institute, Australia
  • Dr Tien Pham, Radiopharmaceutical Research Institute, Australia
  • Dr David Willenborg, Australian National University, Australia
  • Dr Andrew Katsifis, Radiopharmaceutical Research Institute, Australia

    • Objective: The aim of this study was to evaluate the Peripheral Benzodiazepine Receptor (PBR) ligand [123I]CLINDE, in the assessment of microglial/macrophage activation in the CNS of mice during cuprizone induced demyelination and in the rat inflammatory model Experimental Autoimmune Encephalomyelitis (EAE).
    Methods: In the cuprizone model, male C57BL/6J mice were fed cuprizone for 4 weeks or a control diet. Biodistribution, imaging and autoradiographic studies were performed with [123/125I]CLINDE on treated and control mice. In EAE, male Lewis rats were injected in the footpad with myelin basic protein and complete Freund's adjuvant. Eleven days after induction the animals were divided into groups according to disease severity and a score from 0 to 5 assigned. The animals were injected with [123/125I]-CLINDE and the distribution of the tracer evaluated.
    Results: [123I]CLINDE uptake in cuprizone treated mice was significantly higher compared to controls. In vitro autoradiography revealed a 10-fold increase of PBR levels in the corpus callosum (10 times the controls) and significantly higher uptake in other areas of the brain. Higher uptake of [123I]-CLINDE was also observed in all EAE animals compared to controls. The enhanced uptake reflected the ascending nature of the inflammatory lesions ie. uptake in the lumbar > thoracic > cervical > medulla > cerebellum. Also, the uptake of [123I]-CLINDE in the lumbar and thoracic spinal cord correlated with disease severity.
    Conclusion: Neuronal PBR receptors are increased in the brains of cuprizone fed mice and in EAE and that [123I]CLINDE may be a suitable imaging agent for neuroinflammation.

    Conference Organiser - ICMS Pty Ltd