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

Short Term and Long Term Biodistribution of C14-Zoledronic Acid in Rats*

  • Divesh Kumar, Department of Nuclear Medicine, The Children's Hospital at Westmead and University of Sydney, Australia
  • Clin A/Prof Vijay Kumar, Department of Nuclear Medicine and P.E.T., Westmead Hospital, Sydney and University of Sydney, Australia
  • Clin A/Prof David Little, Department of Biotechnology and Orthopaedics, The Children's Hospital at Westmead and University of Sydney, Australia
  • Prof Robert Howman-Giles, Department of Nuclear Medicine, The Children's Hospital at Westmead and University of Sydney, Australia

    • Introduction: Bisphosphonates are synthetic analogues of pyrophosphate with a strong ability to bind to bone mineral hydroxyapatite with useful therapeutic and diagnostic options in bone diseases. The simplest form of first generation bisphosphonate (medronate) is used as bone imaging agent. The second-generation bisphosphonate (pamidronate) is currently the standard treatment for hypercalcemia of malignancy and bone metastases.
    Aim: Zoledronic acid (ZA), a third generation bisphosphonate has highly potent therapeutic effect due to inhibition of osteoclast-mediated bone resorption. However, minimal data is available on the biodistribution of ZA. In this study we have evaluated the long-term biodistribution of carbon (14)-ZA in rats.
    Method: 14C- ZA (0.01mg/kg) was injected in growing rats (4-5wks) to determine the biodistribution at different time points:(1,2,8,24 & 48 h) and (1,2,6,12 & 24 wk). Liquid scintillation counting was used to estimate the percentage bone uptake of 14C-ZA. Autoradiography images were obtained to determine qualitative localisation.
    Results: The results showed that between 1 h and 24 h period, there was a measurable increase in bone uptake of 14C-ZA (0.55% ID/g) and 1.67%ID/g), which plateaued at 48h. Between 1 and 24 weeks, the uptake became steadily decreasing, but still retaining small percentage of 14C-ZA (0.1% ID/g)). The autoradiography images further supported the above data, with very little evidence of significant redistribution to new bone areas.
    Conclusion: The results of this study clearly established the short term and long-term biodistribution of 14C-ZA in rats. This would add significant value in understanding the distribution of this agent in patients.

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