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

Abstract

²²³Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of ²²³Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for ²²³Ra-Dichloride in patients to improve understanding of the underlying mechanisms. A compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg ²²³Ra-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. 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 4.0 (range, 1.9-10.9) and 0.15 (0.07-0.39) h^-1 were obtained for transport from plasma to first bone compartment and vice versa. Rate constants from first to second bone compartment and back of 0.03 (0.02-0.06) and 0.008 (0.003-0.011) h^-1 were calculated. Rate constants for individual patients showed no significant difference between patients and treatments. The developed compartmental model suggests that ²²³Ra-Dichloride initially locates at the bone surface and is then incorporated into the bone matrix relatively quickly. This observation could have implications for dosimetry and understanding of the effects of alpha radiation on normal bone tissue. Results suggest that a population model based on patient measurements is feasible.