Presenter: Joanna Nguyen
Doctor of Philosophy, Biomedical Physics
Ryerson University, 2020
Supervisor: Dr. James Grafe
Phosphate binding drugs are crucial in reducing blood phosphate concentrations in individuals with end-stage renal disease (ESRD) to prevent hyperphosphatemia. While many phosphate binding drugs exist, lanthanum carbonate (LaC) has been reported to be better tolerated than previously used calcium- and aluminum-based phosphate binders. However, since large doses ranging up to 3750 mg LaC/day is orally administered to ESRD patients, concerns have been raised as to whether chronic exposure to lanthanum (La) may lead to La toxicity in bone health.
In this thesis, a robust x-ray fluorescence (XRF) detection system was developed and can be potentially used to non-invasively measure La in ESRD patients. The first step in testing the feasibility of the system was by measuring La in a series of bone mimicking hydroxyapatite phantoms doped with known concentrations of La. The sensitivity of the detection system was evaluated by investigating the minimum detection limit of the system. Initially a 90° irradiation detection geometry was utilized but was deemed inadequate for in vivo measurements due to challenges in experimental reproducibility. Therefore, a 180° backscatter irradiation-detection geometry was adopted for measurements going forward. Since it is anticipated that the developed XRF system will be used clinically to measure bone La concentrations in the ESRD population who are administered LaC, interpatient variability such as amount of overlying tissue thickness at the measurement site, bone size and subject-source movement will affect the intensity of the La x-ray signal. Therefore, a correction procedure was investigated to determine whether these factors could be accounted for to allow true bone La concentrations to be determined from in vivo measurements involving living subjects. In addition, since literature data on the natural accumulation of La in bone from the environment and diet is limited, an ex vivo study was performed on excised cadaver tibiae obtained from deceased donors with no known direct exposure to La.
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