©TheCanadian Journal ofUrology™: International Supplement, April 2014
Prostatecancer frequentlymetastasizes to thebone
primarilywithin the axial skeleton (vertebral bodies,
pelvis, ribs, and skull) but may also occur in the
long bones.
12
Radiographically, osseous metastases
are most often noted on
99
technetiummethylene
diphosphonate bone scintigraphy scans. However,
newermodalities such as
18
sodiumfluoride PET and
18
fluorodeoxyglucose PET aremore frequently being
utilizedgiven their increasedsensitivity fordetection.
13
Clinically, bone metastases are the primary cause
of morbidity andmortality for men with metastatic
CRPC,
14
with80%-90%ofpatientseventuallydeveloping
metastatic disease.
15
Bone lesions may cause pain or
skeletalrelatedeventssuchasspinalcordcompression,
fractures,orhypercalcemia. Further,theextentofosseous
involvement isassociatedwithoverallsurvival.
16
Given
the systemic and complexnatureofmanagingpainful
bonemetastases, radiopharmaceuticals have emerged
asapromisingmodality.
The current radiopharmaceutical agents used
againstmetastaticprostatecancerincludestrontium-89,
samarium-153, rhenium-186, and radium 223. The
physical characteristics of these agents are shown in
Table 1. Multiple randomized controlled trials have
beenconductedwith theseagents for themanagement
of prostate cancer patients with bonemetastases.
17-33
Historically,primaryoutcomes includedpainresponse,
decrease inanalgesicconsumption,andquality-of-life.
Radium 223 is the first radiopharmaceutical agent to
demonstrate improved survival amongpatientswith
symptomatic bone-metastaticCRPC.
32
This review will provide an overview of
radiopharmaceuticals in prostate cancer with a
focus on the mechanism of action of alpha and beta
emitters. Further, itwillhighlightradium223,Figure1,
including the indicationsbasedon theclinical trials,
29-33
administration,andstrategiestomanagethesideeffects
of therapy.
Alpha, beta, andgamma emission
Radioactive decay, also known as radioactivity, is the
process by which the nucleus of an unstable isotope
loses energy through emission of particles of ionizing
radiation. Radiationmaybe emitted in the formof an
alpha (
α
) or beta (
β
) particle, a gamma (
γ
) ray or any
combination. An
α
particle consist of twoprotons and
twoneutrons,a
β
particleisahighenergyelectron,while
a
γ
rayisdescribedasionizingelectromagneticradiation.
Each type of radiation has different advantages and
disadvantages.
Alpha particles have the shortest range of these
particle types, resulting inadensedepositionofenergy
close to the origin of the particle emission. Thus,
α
particles providemore dense ionizing radiation over
ashorterdistance<100µm (approximately2-10 tumor
cell diameters), resulting in the induction of DNA
double-strandbreakswithminimizedmyelotoxicity.
30
Alpha particles can be stopped by a sheet of paper,
eliminating the need for any radiation shielding.
Radium 223, as an alpha emitter, administered
intravenouslyrequiresnoradiationsafetyprecautions
TABLE 1.
Physical characteristicsof radiopharmaceuticalsused inprostate cancer
Radionuclide
Half-life
Decayparticle
Tissuepenetration
Radium223
11.4days
alpha
< 0.1mm
Strontium 89
50.5days
beta
5.5mm
Samarium 153
1.9days
beta, gamma
2.5mm
Rhenium 186
3.8days
beta, gamma
4.5mm
Figure1.
Overviewschematicofradium223mechanism
of action.
71
DenETAL.
