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

Synthesis and Evaluation of Novel [123I] and [18F] Labelled Pyrazolopyrimidines, for the Study of Peripheral Benzodiazepine Receptor using PET and SPECT

  • Dr Chris Fookes, Radiopharmaceutical Research Institute, Australia
  • Ms Taryn Homes, University of Wollongong, 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
  • Prof Paul Keller, University of Wollongong, Australia
  • Dr Andrew Katsifis, Radiopharmaceutical Research Institute, Australia

    • Objective: The aim of this study was to synthesise and evaluate the pyrazolopyrimidine ligands [18F]PBR099, [18F]PBR146 and [123I]PBR215 for the study of Peripheral Benzodiazepine Receptors (PBR) using PET and SPECT.
    Methods: Several pyrazolopyrimidine structures were prepared incorporating the radionuclides fluorine-18 and iodine-123. F-18 radiolabelling of PBR099 and PBR146 were prepared from the tosyloxy precursor. The I-123 analogue was prepared by iododestannylation reaction.
    Biodistribution and tissue analysis was performed in rats. Competition studies using PK11195, Ro5-4864 and Flumazenil were undertaken to assess tracer specificity and selectivity. Metabolite analysis was performed to confirm the integrity of the administered tracer in specific PBR tissue and plasma.
    Results: The IC50 of PBR099, PBR146 and PBR215 are 15, 8.3 and 16.5 for the PBR and >5000 nM for the CBR. PBR099 and PBR146 were synthesised in 30-40% while PBR215 was 55-65% radiochemical yield uncorrected and with > 95 % radiochemical purity. The uptake of 18F]PBR099 [18F]PBR146 and [123I]PBR215, followed the known distribution of PBR density in vivo. High uptake was observed by all tracers in the adrenals, heart, kidney and olfactory bulbs of the brain. Pre-treatment with PK 11195 and Ro 5-4864 decreased the uptake of all tracers in peripheral organs except in the adrenals which showed an increase. In the olfactory regions a significant decrease was observed with PBR215, while an increase was observed with PBR099 and no change with PBR146. Flumazenil had no effect in the uptake of tracers.
    Conclusion: The pyrazolopyrimidine structures provide an excellent scaffold for development of novel PBR ligands.

    Conference Organiser - ICMS Pty Ltd