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Radiopharmacokinetic modelling and radiation dose assessment of 223Ra used for treatment of metastatic castration resistant prostate cancer.

EJNMMI Phys. 8:44 (2021)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag

Purpose

Ra-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 and dosimetric framework developed by the International Commission on Radiological Protection (ICRP) and to show their radiopharmacokinetic behaviour. Organ absorbed and equivalent doses after intravenous injection of 223Ra were estimated and compared to clinical data and other modelling study.

Methods

The most recent ICRP systemic biokinetic model of 223Ra and its progeny 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 was assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, 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 values to estimate the organ absorbed and equivalent doses.

Results

The 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 clinic trials. The highest absorbed dose coefficients were found for bone endosteum, liver, and red marrow, followed by kidneys and colon.

Conclusion

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 from clinical studies and of a previous compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter radiopharmaceutical, biokinetic models, 223Ra, internal dose, radionuclide therapy; Bone Metastases; Radium-223; Dosimetry; Ra-223-dichloride; Pharmacokinetics; Biodistribution; Emitters; Software; Therapy
ISSN (print) / ISBN 2197-7364
e-ISSN 2197-7364
Zeitschrift EJNMMI Physics
Quellenangaben Band: 8, Heft: 1, Seiten: , Artikelnummer: 44 Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Begutachtungsstatus Peer reviewed
Förderungen Projekt DEAL
Helmholtz Zentrum Munchen-German Research Center for Environmental Health (GmbH)