Abstract
PurposeRa-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study.MethodsThe 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. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, overset{sim }{a}left({r}_S,{T}_Dright), in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned overset{sim }{a}left({r}_S,{T}_Dright) values.ResultsThe distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon.ConclusionThe biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.
Highlights
Worldwide, prostate cancer is the second most frequent cancer in men [1]
The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®
The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study
Summary
Prostate cancer is the second most frequent cancer in men [1]. 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 [2]. 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. Several clinical trials using Xofigo® were performed in order to demonstrate the pharmacokinetic behaviour of 223Ra in the human body after its intravenous injection and to estimate organ absorbed doses in radiation-sensitive organs and tissues, such as bone surface and red marrow [8,9,10,11]. The improved systemic model of radium is a modification of the previous model of ICRP Publication 67 [13]. It can be assumed that the ICRP systemic model for workers and members of the public applies to ingestion but () to materials taken up by blood in general. The model is applicable to the Radionuclide 223Ra ➔ 219Rn
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