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A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of Ra-223-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases

Chittenden, Sarah J.; Hindorf, Cecilia LU ; Parker, Christopher C.; Lewington, Valerie J.; Pratt, Brenda E.; Johnson, Bernadette and Flux, Glenn D. (2015) In Journal of Nuclear Medicine 56(9). p.1304-1309
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 Ra-223-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Methods: Six patients received 2 intravenous injections of Ra-223-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... (More)
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 Ra-223-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Methods: Six patients received 2 intravenous injections of Ra-223-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 a 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dosimetry, Ra-223, biodistribution, molecular radiotherapy, alpha-emitter
in
Journal of Nuclear Medicine
volume
56
issue
9
pages
1304 - 1309
publisher
Society of Nuclear Medicine
external identifiers
  • wos:000361153000011
  • scopus:84940974848
ISSN
0161-5505
DOI
10.2967/jnumed.115.157123
language
English
LU publication?
yes
id
9fb671cc-5418-4635-b60a-fe8d188689e8 (old id 8077271)
date added to LUP
2015-10-23 11:59:32
date last changed
2017-10-22 04:01:15
@article{9fb671cc-5418-4635-b60a-fe8d188689e8,
  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 Ra-223-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Methods: Six patients received 2 intravenous injections of Ra-223-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 a 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       = {Chittenden, Sarah J. and Hindorf, Cecilia and Parker, Christopher C. and Lewington, Valerie J. and Pratt, Brenda E. and Johnson, Bernadette and Flux, Glenn D.},
  issn         = {0161-5505},
  keyword      = {dosimetry,Ra-223,biodistribution,molecular radiotherapy,alpha-emitter},
  language     = {eng},
  number       = {9},
  pages        = {1304--1309},
  publisher    = {Society of Nuclear Medicine},
  series       = {Journal of Nuclear Medicine},
  title        = {A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of Ra-223-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases},
  url          = {http://dx.doi.org/10.2967/jnumed.115.157123},
  volume       = {56},
  year         = {2015},
}