Exhalation of Rn-219 by patients treated with Radium-223

Treatment with Ra-223 dichloride is approved for the therapy of castration resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases in Europe since 2013, and Ra-223 is under discussion for labelling other molecules and nanoparticles. The direct progeny of Ra-223 is Rn-219, also known as actinon, a radioactive noble gas with a half-life of 3.98 s. This Rn-219 can be exhaled by patients while Ra-223 is present in the blood. Hence, direct measurements for assessing the exhalation of Rn-219 were performed for the first time in the context of the non-interventional multicenter study "RAPSODY", a substudy to the international early access program, which aimed at assessing the radiation exposure of relatives of patients suffering from castration resistant prostate cancer with bone metastases and treated with Ra-223 dichloride in an outpatient setting, in order to investigate if this kind of method is functional and tolerated by the patients.

Rn-219 was measured directly in patients' exhalations using Alphaguard radon monitors (Saphymo, formerly Genitron, Frankfurt, Germany), originally intended for the measurement of Rn-222, and custom-made breath-test kits. Measurements were performed 20-30 min p. i. and 3-4 h p. i. In total, datasets from 21 administrations in 14 patients were obtained.

Although 75% of the measurement data 20-30 min p. i. and 35% of the measurement data 3-4 h p. i., respectively, were censored due to exceedance of the upper limit of the Alphaguards' measurement range in the applied measurement setup, statistical data were derived based on the assumption of lognormal distributions. For measurements 3-4 h p. i., mean activity concentrations of Rn-219 in exhaled breath of approx. 4.4 kBq/l were obtained. In measurements 20-30 min p. i., the expectation value of the activity concentration of approx. 6 kBq/l, derived by statistical methods, was higher.

Direct measurements using Alphaguard instruments are suitable for assessing the exhalation of Rn-219 by patients treated with Ra-223. The measurement method is well tolerated by the patients. Rn-219 is present in patients' exhalations. Our results are in accordance with published data obtained using other, indirect measurement methods.