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

The Peripheral Benzodiazepine Receptor Ligand ClINME can Delineate Microglial Activation Similarly well with either SPECT or PET

  • Dr Mitchell Quinlivan, Australian Nuclear Science and Technology Organisation, Australia
  • Dr Marie-Claude Gregoire, Australian Nuclear Science and Technology Organisation, Australia
  • Ms Filomena Mattner, Australian Nuclear Science and Technology Organisation, Australia
  • Dr Andrew Katsifis, Australian Nuclear Science and Technology Organisation, Australia

    • Objectives: Recently the PET ligand [11-C]ClINME was reported to demonstrate better than [11-C]PK11195 the Peripheral Benzodiazepine Receptor expression associated with microglial activation following an excitotoxic lesion (Glia, 55:1459). Here, we evaluated the efficacy of [123-I]ClINME for the measurement of this same lesion, using high-resolution Pinhole SPECT.

    Methods: Microglial activation was induced in male, SD rats with a unilateral injection of 7.5 nmol [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid into the striatum. After 8 days, SPECT and CT images were acquired (X-SPECT; GMI, Northridge, USA) and ROIs drawn over the lesion and the contralateral striatum using the co-registered images. Post-mortem studies included in vitro [125-I]ClINME autoradiography and immunohistochemistry (IHC).

    Results: SPECT quantitation gave ratios of 1.9 – 3.0 between [123-I]ClINME uptake in the lesioned vs non-lesioned striatum. This range encompasses that reported for [11-C]ClINME (2.14) and that found here with [125-I]ClINME in vitro autoradiography (2.10), and is higher than that reported for [11-C]ClINME PET (1.62). IHC here confirmed profound neuronal loss and astrocytic and microglial activation on the lesioned sided.

    Conclusions: Following previous work demonstrating the superior imaging qualities of [11-C]ClINME in PET, this study shows [123-I]ClINME to be similarly able to depict IHC-confirmed microglial activation. Radiolabelled ClINME thus has the potential, with either PET or SPECT, to be a clinically-useful marker of neurodegenerative diseases such as Alzheimer’s disease.

    Conference Organiser - ICMS Pty Ltd