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

Synthesis and Evaluation of [18F]PBR102 and [18F]PBR111. Novel Ligands for Imaging Neurodegeneration and Inflammation using PET

  • Dr Chris Fookes, Radiopharmaceutical Research Institute, Australia
  • Dr Tien Pham, Radiopharmaceutical Research Institute, Australia
  • Ms Filomena Mattner, Radiopharmaceutical Research Institute, Australia
  • Dr Ivan Greguric, Radiopharmaceutical Research Institute, Australia
  • Dr Xiang Liu, Radiopharmaceutical Research Institute, Australia
  • Ms Paula Berghofer, Radiopharmaceutical Research Institute, Australia
  • Dr Rachael Shepherd, Radiopharmaceutical Research Institute, Australia
  • Dr Andrew Katsifis, Radiopharmaceutical Research Institute, Australia

    • Objectives: The aim of this study was to synthesise and evaluate the novel imidazopyrdine based Peripheral Benzodiazepine Receptor (PBR) ligands [18F]PBR102 and [18F]PBR111 for the assessment of microglial/macrophage activation in the CNS.
    Methods: Two imidazopyrine based ligands PBR102 and PBR111 were radiolabelled with F-18 as the [18F]fluoroethyl and [18F]fluoropropyl derivatives respectively via the tosyloxy precursors followed by HPLC purification.
    The biodistribution of the above tracers was performed in rats. Competition studies using PK11195, Ro5-4864 and Flumazenil (1 mg/kg) were undertaken to assess tracer specificity and selectivity. Metabolite analysis was performed to confirm the integrity of the administered tracer in specific organs and in plasma.
    Results: The IC50 of 18F]PBR102 and [18F]PBR111 are 13.2 and 7.5 for the PBR and >1500 nM for the CBR. [18F]PBR102 and [18F]PBR111 were synthesised in 40-55% radiochemical yield and >95% radiochemical purity. The uptake of [18F]PBR102 and [18F]PBR111 followed the known distribution of PBR density with high uptake observed by both tracers in the adrenals, heart and kidneys. The uptake of [18F]PBR102 in the olfactory bulbs ranged from 0.56 % at 15 min to 0.40 % ID/g at 4 h PI compared to 0.64% to 0.41% at 15 min and 4 h for [18F]PBR111. Preadminsitration of PK11195 led to a significant reduction of activity with [18F]PBR111 but not with [18F]PBR102. No effects were observed with flumazenil.
    Conclusion: [18F]PBR111 displayed favourable kinetics in rats with a high degree of non-specific binding suitable for further development as an imaging agent for PBR associated disorders.

    Conference Organiser - ICMS Pty Ltd