©TheCanadian Journal ofUrology™: International Supplement, April 2014
such as particular sleeping arrangements, limited
time or specified distance from children or pregnant
women.
Incontrast toalphaparticles,
β
emittershave track
lengths that consist of up to a fewmillimeterswhich
results in collateral bone marrow toxicity. Further,
β
particles require increased shielding as they can
penetrate paper, but can be stopped by a thin layer
of high Zmaterial depending on the energy of the
particle. Consequently,
β
emitters are often stored in
lead-shieldedcontainers toreduceradiationexposure;
however patients still have little to no radiation
precautions or restrictions.
Bonephysiology and cancer
Bone homeostasis is a complex cellular process
consisting of osteoblasts, which function in bone
production and mineralization, and osteoclasts,
which function in bone resorption.
34
Bonematrix is
initiallyorganicosteoidwhosecalciumhydroxyapatite
mineralization occurs through alkaline phosphatase
function. Cancercellscause inappropriateosteoblastic
or osteoclastic activity resulting in either blastic or
lytic lesions respectively.
35
Blastic function can be
monitored clinically via alkaline phosphatase levels.
The current radiopharmaceuticals either mimic
calcium (radium, strontium)orbindasanattachment
to thehydroxyapatite componentsof thebonematrix
(samarium, rhenium).
36
Current radiopharmaceuticals: indications
andbenefits
Strontium-89
Strontium-89 is a calcium analog approved by
the FDA in 1993 for the treatment of painful bone
metastases.
37
It decays as a pure
β
emitter with only
0.01%
γ
emission and is incorporated into bonewhen
intravenously administered. Strontium has a 10-fold
uptake increase intobonecontainingmetastatic tumor
as compared to normal healthy bone.
38
There have
beenmultiplerandomizedtrialsevaluating theefficacy
of strontium-89withmost focused onpain reduction.
However, inter-study comparison is limitedgiven the
variousgradingsystemsutilized. Asystematic review
of strontium-89 reported a complete pain response
varying from 8% to 77%with a partial pain response
in 44% of patients.
39
In addition, use of analgesic
decreasedby70%-80%anddurationofclinicalresponse
variedfrom3-6months. Thecommontoxicities include
leukopenia, thrombocytopenia with nadir in counts
occurringapproximately4-8weekspost injection.
Samarium-153 lexidronam
Samarium-153, a
β
emitterwith 28%
γ
emission, was
approved by the FDA in the 1997 for the treatment
of bonemetastases. The radionuclide has a half-life
of 1.9 days and is complexedwith ethylene diamine
tetramethylenephosphonate (EDTMP)whichrapidly
localizes tobone inassociationwithhydroxyapatite. It
has afive times greater affinity to tumor thannormal
bone. It isdelivered intravenouslyandhasacomplete
renal clearance within 6 hours of administration.
40
Multiplerandomizedphase III trialshaveconsistently
demonstrated an improvement in bone pain and
reduced analgesic use.
24-26
As with strontium-89,
myelosuppresion, particularly thrombocytopenia, is
themost common side effect.
Rhenium-186 etidronate
Rhenium-186 hydroxyethylidene diphosphonate
(HEDP) a
β
and
γ
emitter, has a half-life of 3.7 days.
Its
γ
emission allows for bonemetastases localization
though imaging, making it both diagnostic and
therapeutic. Rhenium has efficacy inpain reduction
with thrombocytopeniaand leukopeniabeing themost
common toxicities.
27,28
Comparison of beta emitters
These compounds have been compared in the
management of patients with osteoblastic lesions to
determine their relative efficacy. While all effective,
there was no statistical significance between the
various agents in terms of pain palliation, analgesic
use, or bonemarrow toxicity.
41-43
Radium 223
Radium223was recentlyapprovedby theFDA in2013
for the management of men withmetastatic castrate
resistant prostate cancer after the publication of a
randomized phase III trial which showed an overall
survival benefit.
32
Table 2 provides the indications,
administration, and strategies tomanage side effects.
Radium 223, an alpha particle emitter, was originally
selected given its half-life (11.4 days) that allowed
convenientdosing,saferadondaughterisotopeandhigh
skeletaluptakeinpatientswithosteoblasticmetastases.
44
The phase I dose escalation study of radium 223
consistedof25breastandprostatecancerpatientswith
osteoblastic lesionswhowere injectedwithasingledose
of the agent.
30
Pharmacokinetic studiesdemonstrated
thatwithin24hours<1%ofadministereddoseremained
in circulation andwas predominantly eliminated via
the gastrointestinal tract. Pain relief was reported by
52%, 60%, and 56% of patients after either 1, 4, or 8
weeks respectively. Twenty-eight percent of patients
72
Practical guide to theuseof radium 223dichloride
