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

Pharmacological Evaluation of the Peripheral Benzodiazepine Receptor Radioligand [123I]CLINDE in Animal Tumour Models

  • Ms Filomena Mattner, Radiopharmaceutical Research Institute, Australia
  • Ms Paula Berghofer, Radiopharmaceutical Research Institute, Australia
  • Dr Rachael Shepherd, Radiopharmaceutical Research Institute, Australia
  • Mr Nicholas Howell, Radiopharmaceutical Research Institute, Australia
  • Dr Tien Pham, Radiopharmaceutical Research Institute, Australia
  • Dr Thomas Bourdier, Radiopharmaceutical Research Institute, Australia
  • Ms Patrice Ballantyne, Radiopharmaceutical Research Institute, Australia
  • Dr Andrew Katsifis, Radiopharmaceutical Research Institute, Australia

    • Objective:
    The aim of this study was to evaluate the peripheral benzodiazepine receptor ligand [123I]-CLINDE in tumour bearing rodents.

    Method:
    Human melanoma A375 cells and human breast adenocarcinoma, MDA-MB-231 cells were injected subcutaneously in Balb/c nude mice. Biodistribution studies were undertaken 24 and 36 days after injection. Rat mammary adenocarcinoma cells (MAT) were injected subcutaneously in Fisher rats and evaluated after 12 days. PBR expression in tumours was assessed by ligand binding assays and immunohistochemistry. Imaging was performed on SPECT animal imaging system.

    Results:
    PBR binding of [125I]CLINDE in tumours indicated high affinity PBR expression (Kd =1nM) and Bmax of 22, 18 and 11 pmol/mg protein for MAT, A375 and MDA, respectively. PBR expression in the tumours was confirmed by immunohistochemistry. Biodistribution in A375 tumour mice indicated high [123I]CLINDE uptake (2.5-3.0% ID/g) which was retained to at least 48h. MDA tumour uptake was 0.9-1.6%ID/g. The tumour to blood ratio (T/B) in both models was 7 at 24h. MAT tumour uptake in rats showed a similar pattern with a peak of 0.9-1 %ID/g also retained over 48 h with T/B of 12. Pre-administration of PK 11195 reduced the uptake of activity in all tumours. γ-Imaging of [123I]CLINDE in Fisher rats indicated significant contrast in the tumours compared to normal tissue. Metabolite studies indicated that the activity extracted from tumours was the intact tracer.

    Conclusion:
    The imidazopyridine, [123I]CLINDE, labelled with either iodine-123 or other PET isotopes are promising ligands for the study of the PBR in a variety of tumours.

    Conference Organiser - ICMS Pty Ltd