After intravenous administration of 223Ra, its bone-seeking and alpha-particle emitting properties may reduce bone pain, thereby improving the quality of life of the patients. The short alpha particle path range (< 100 μm) may minimise damage to the surrounding normal tissue. 223Ra is an alpha-emitter (physical half-life 11.4 days) with a high linear energy transfer (80 keV/μm) which may lead to a high frequency of double-strand DNA breaks in tumour cells this may result in a highly localised cytotoxic effect to tumour cell death. Radium (Ra, 223Ra) behaves similar to calcium after its intravenous injection into the human body and its main target is the bone at areas of active bone formation, thereby forming complexes with the bone mineral hydroxyapatite. The bone metastases can result in severe bone pain and symptoms like pathologic fractures, spinal cord compression or myelosuppression. In 2013, 223Ra-dichloride ( 223Ra, Xofigo®, Bayer) was approved by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) as a tolerated radiopharmaceutical for treatment of patients suffering from castration-resistant prostate cancer with bone metastases and no visceral metastases. Worldwide, prostate cancer is the second most frequent cancer in men. The dose to the bone endosteum was found to be lower by a factor of ca. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon. Similar tendencies were observed in clinical trials of other authors. Bone retention was found to be about 30% at 4 h post-injection. The distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion.
The time activity curves for 223Ra were modelled and the time integrated activity coefficients, \( \overset_D\right) \) values. Independent kinetics were assumed for the progeny of 223Ra. The most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour.
Ra-223 dichloride ( 223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer.
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