Baylor University Medical Center Proceedings October 2017 - 424

Usefulness of radium-223 in patients with bone metastases
Nishant Gupta, MD, Arushi Devgan, MBBS, Itisha Bansal, MD, Thomas D. Olsavsky, MD, Shuo Li, MD,
Ahmed Abdelbaki, MD, and Yogesh Kumar, MD

Castration-resistant prostate osseous metastases can be challenging
to treat. There is a new era of clinical advancement with the Food and
Drug Administration approval of radium-223 for use in these patients.
Radium-223 is the only clinically used therapeutic radiopharmaceutical that emits alpha particles, making it extremely safe for therapeutic
purposes for the patient as well as close contacts. This review discusses
radium-223's mechanism of action, pharmacokinetics, indications, and
safety profile, as well as findings of concluded clinical trials.

rostate cancer is the most common malignancy in men
in the United States and Europe and is the third leading cause of cancer-related death in men. Nearly 14%
of men will be diagnosed with prostate cancer at some
point in their life. In 2014, prostate cancer accounted for 24%
and 27% of all new male cancer cases in Canada and the US,
respectively (1, 2). About 85% of cases present with localized
disease, but nearly 40% progress to metastatic cancer. Bone
metastases can be present in more than 90% of patients with
advanced prostate cancer, leading to signiﬁcant morbidity and
mortality (3, 4). Patients are initially treated with either chemical or surgical androgen deprivation therapies. However, there
is inevitable progression to castration-resistant prostate cancer
(CRPC), which develops despite castration levels of testosterone. When this disease presents with detectable macroscopic
metastases, patients are considered to have metastatic CRPC
(mCRPC), which has a poor prognosis and an expected survival
of 18 to 20 months. Complications include signiﬁcant bone
pain, skeletal-related complications such as pathologic fractures,
malignant hypercalcemia, bone marrow suppression, and spinal
cord compression (5-7).
MECHANISM OF ACTION AND RADIOBIOLOGY OF RADIUM-223
Radium 223 dichloride (radium-223), an alpha-emitting
radionuclide, was the ﬁrst agent of its kind to be approved by the
US Food and Drug Administration (FDA) following the 2013
ALSYMPCA trial for treatment of bone pain in patients with
mCRPC. It has a half-life of 11.4 days. Radium-223 decays to
4 alpha particles for every atom. It is a calcium mimic that binds
to hydroxyapatite and induces double-stranded breaks in DNA
(8, 9). The short range of particles emitted and the high linear
424

energy transfer lead to intensive killing in a small tissue volume,
thereby sparing more of the normal bone (10). Its eﬀect is a
combination of decreased pathologic bone turnover and tumor
irradiation (11). Other bone-seeking radiopharmaceuticals like
the beta-emitting strontium-89 and samarium-153 ethylenediamine tetramethylene phosphonic acid have also been used
for bone therapy, but have not been found to increase overall
survival (12, 13).
PHARMACOKINETICS
Radium-223 is taken up primarily by bone tissue and bone
metastases rapidly after intravenous injection. Most of the agent
(95%) is eliminated from the body by the fecal route; ∼5% is
excreted in urine. Therefore, any changes in intestinal transit can
aﬀect the elimination rate of radium-223. It is not metabolized
by the liver (1).
SAFETY PROFILE
Data collected from more than 1000 patients in phase 2 and
3 trials comprise the basis for the drug's safety proﬁle (1). Data
from a 3-year follow-up study have also shown that radium-223
therapy is both safe and well tolerated (14). However, combining radium-223 with chemotherapy is not recommended because of potential additive eﬀects of bone marrow suppression.
The most common adverse reactions observed were nausea,
vomiting, diarrhea, and peripheral edema. Radium-223 can
cause hematologic abnormalities like anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Anemia
and thrombocytopenia were the most common reasons for discontinuation of the drug (15). Concurrent administration of

From the Department of Radiology, Columbia University Medical Center, New York,
New York (Gupta); Department of Radiology, University of Arkansas, Little Rock,
Arkansas (Devgan); Department of Anesthesiology, New York-Presbyterian Brooklyn
Methodist Hospital, Brooklyn, New York (Bansal); Department of Nuclear Medicine,
St. Vincent's Medical Center, Bridgeport, Connecticut (Olsavsky); Department of
Radiology, Yale New Haven Health at Bridgeport Hospital, Bridgeport, Connecticut (Li,
Abdelbaki); and Columbia University at Bassett Healthcare, Cooperstown, New York
(Kumar).
Corresponding author: Nishant Gupta, MD, Department of Radiology, Columbia
University Medical Center, 622 W. 168th Street, New York, NY 10032 (e-mail:
drngupta20@gmail.com).
Proc (Bayl Univ Med Cent) 2017;30(4):424-426

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