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Abstract

The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of (223)Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer.

METHODS:

Six patients received 2 intravenous injections of (223)Ra-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events.

RESULTS:

The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from α emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver.

CONCLUSION:

A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity on the bone surfaces. 

Author information

Chittenden SJ1, Hindorf C2, Parker CC3, Lewington VJ4, Pratt BE5, Johnson B3, Flux GD5.​

1Joint Department of Physics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom sarah.chittenden@icr.ac.uk.

2Department of Radiation Physics, Radionuklidcentralen, Skåne University Hospital Lund, Lund, Sweden.

3Department of Urology, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; and.

4Department of Nuclear Medicine, Guy's Hospital, London, United Kingdom.

5Joint Department of Physics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom.