Compartmental Model for 223Ra-Dichloride in Patients With Metastatic Bone Disease From Castration-Resistant Prostate Cancer

Abstract

A better understanding of the uptake mechanisms of 223 Ra-Dichloride is essential for patient-tailored treatment planning and to improve understanding of the effects of alpha radiation on bone tissue. The developed compartmental model suggests that 223 Ra-Dichloride locates on the bone surface and is incorporated into the bone matrix. Those findings could have implications for bone marrow dosimetry and can be used to further investigate the effects of alpha Purpose: 223 Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of 223 Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for 223 Ra-Dichloride in patients to improve understanding of the underlying mechanisms. Methods and Materials: A compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg 223 Ra-Dichloride) for plasma, bone surfaces, small intestines, large intestines, and excretion data. Rate constants were extracted. Rate constant variability between patients and treatments was assessed. A population model was proposed and compared with the established International Commission on Radiological Protection-67 compartmental model. Results: A single bone compartment cannot accurately describe activity retention in the skeleton. The addition of a second bone compartment improved the fit to skeleton retention data, and the Akaike information criterion decreased. Mean rate constants of 4.

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

“…This reflects the difference between the 223 Ra uptake into tumour lesions and normal bones. Taprogge and co-workers [ 30 ], who analysed data of six patients from Chittenden et al [ 10 ], are in the process of developing a simple compartmental model for plasma, bone surfaces, small, and large intestines and excretion path that better fits to the patient data. Carrasquillo et al [ 11 ] observed a small amount (not quantified) of activity in kidneys and liver, but only early after injection (< 4 h post-administration).…”

Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases

“…The absorbed radiation dose to the intestine during absorbing 223 Ra though the intestine was not considered in the Phase I study. Actually, in a proposed compartmental model for 223 Ra by Taprogge et al, 223 Ra was excreted into faces without the reabsorption from the small intestine 21 . However, some 223 Ra in the intestine must be absorbed into the blood, and the alpha-particles emitted from 223 Ra on absorption should, in theory, harm the intestinal cells.…”

Radioimmunotherapy for Brain Metastases: The Potential for Inflammation as a Target of Choice

“…Nevertheless, a substantial effort is being made to individualise patient treatments and to improve the accuracy of dosimetry procedures in the clinic. Important initiatives to standardise dosimetry include the internal dosimetry task force linked to EANM ( 29 , 30 ), the Medical Internal Radiation Dose committee ( 31 ), or the EU consortium MEDIRAD ( 32 , 33 ). Dosimetry should play an important role when a new agent for RIT undergoes clinical testing, alongside the assessment of the maximum tolerated dose and side effects, similar to clinical trials of nonradioactive oncological drugs ( 34 ).…”