Download Dopamine Transporter (DaT) SPECT Imaging

m i
gateway
Vol. 6 • Issue 1 • 2012•1
THE NEWSLETTER OF THE SNM CENTER FOR MOLECULAR IMAGING INNOVATION AND TRANSLATION
Dopamine Transporter (DaT) SPECT
Imaging
IN THIS ISSUE
FDA Moves Forward on Imaging
I-ioflupane (N-ω-fluoropropyl-2β- where the dopamine transporters are lo- kinsonism and neuroleptic drug-induced
carbomethoxy-3β-(4-iodophenyl)
on the presynaptic side of dopami- parkinsonism, however, thereLitBriefs
is no presyn2
Amyloid innortrothecated
Brain
pane), is a single photon emission com- nergic synapses (Figure 2). They transport aptic dopaminergic degeneration and DaT
123
T
puted tomography (SPECT)
molecular
dopamine
out of theadvances
synaptic incleft,
back
he past several
years have
seen tremendous
the deimaging agent for imaging the dopamine into presynaptic axons for either re-use or
velopment of new radiopharmaceuticals for molecular imaging with
transporter (DaT) (Figure 1). It was recent- degradation.
positron
emission
(PET). Despite
numberneuof
ly approved by the
U.S. Food
and tomography
Drug
Degeneration
of the
theselarge
presynaptic
Administration (FDA)
and is and
available
in rons
pre-clinical
early clinical
studies
in the
literature,
however,
only
results
in lower
striatal
DaT density.
the U.S. market. This agent was approved Parkinsonian symptoms typically become
Continued on page 2. See FDA.
in Europe in 2000, and several hundred apparent only after at least 50 percent of
thousand patients have been scanned. It nigrostriatal nerve terminals are lost. Thus,
has proven to be safe, reliable and very DaT imaging is excellent for early detection
sensitive for detection of degeneration of of nigrostriatal dopaminergic degeneration.
nigrostriatal nerve cells in the differential Also, the degree of reduction in DaT binddiagnosis of movement disorders such as ing is related to disease severity.
Parkinson’s disease (PD) and dementia.
In PD and related parkinsonian synAlthough clinical diagnosis is straightfor- dromes such as multiple system atrophy
ward in many patients, it may be difficult (MSA) and progressive supranuclear palsy
in others—especially
in of
early
disease—and
thereofisinsudated
presynaptic
olecular imaging
various
compo- (PSP),
scavenging
lipid,dopaminergic
oversee their
structural
imaging
with
computed
tomogtherefore
nents of atherosclerotic plaques has
been degeneration
transformationand
to foam
cells decreased
or mediateDaT
cell
raphy
or magnetic
resonance
imaging
usu- binding.
proposed,
and proof
of principle
has been
death (1).Although the pattern of DaT bindally
is of little help.
tends to betargets
somewhat
there
demonstrated
in experimental models of ing Molecular
have different,
also included
123
I-iofl
is a cocaine
analogue
a large
overlap
in DaT imaging
disease
(1). upane
These preclinical
studies
have is
events
that
are associated
with orfindings
consewith
high affinity
and relatively
selec- among
these
syndromes, and
I-iofl
upane
predominantly
targeted
plaquegood
inflammaquent to
inflammation,
such123as
productivity
for
DaT.
DaT
concentration
is
highest
is unable and
to discriminate
among
tion with the premise that the extent of imaging
tion of cytokines
metalloproteinases.
in
striatum (putamen
and caudate
In essential
psychogenic
parinflammation
would determine
thenucleus)
vulner- them.
Although
these tremor,
experimental
molecular
ability of the plaque to rupture. Plaque in- imaging studies have offered significant
flammation has been detected by targeting promise, translational data in the clinical
alterations in monocytes that facilitate their setting has just started to emerge. Clinical
migration to the neointima, ensure efficient studies of molecular targeting are the major
Clinical Feasibility of Molecular
Imaging of Plaque Inflammation
in Atherosclerosis
M
Imaging
Training
TheMolecular
likelihood that atherosclerotic
plaques
will result in acute vascular
Course Debuts
events is intimately associated with the morphologic traits of the plaque
A
s we all know, nuclear medicine is rapidly evolving. Molecular imaging, including
and thenon-radioactive
extent of inflammation.
tracers, is becoming an increasingly important part of our specialty.
As a result, the Society of Nuclear Medicine (SNM) refocused its mission to incorporate
the
expanding
role of review.
molecular imaging in patient
care
and islipoproteins
now considering
a name
focus
of the following
tion and
labeled
to trace
their
change
to
the
“Society
of
Nuclear
Medicine
and
Molecular
Imaging.”
We have referred to some of the early destination in the inflammatory cells in
With this
new mission,
Center
for Molecular
Imaging
Translamolecular
imaging
attemptsthe
that
labeled
plaques (1).
Even Innovation
though theand
incorporation
Education
Task
Force
has
examined
the
educational
needs
for
current
and
white blood cells to follow their localiza- tion of radiolabeled components infuture
the
physicians and scientists practicing molecular imaging. Suggestions were developed for
Continued on page 3. See MI Training.
MI in the News
4
SPECT is normal.
123
SNM can
to Sponsor
5
I-ioflupane SPECT
also be used
to differentiate dementia with Lewy bodies
New RECIST Guidelines
6
(DLB) from other dementias. This can be
7
MI DLB
Journalpatients
important clinically, because
8
MI Calendar
Indications for
I-ioflupane imaging
123
plaque
may ofnot
been adequate,
• Detection
losshave
of functional
dopaminergicthese
neuron
terminals
in the striatum
of patients
studies
created
a sound
foundation
for the
with clinicallyofuncertain
parkinsonian
syn-of the
development
imaging
strategies
dromes
future.
• Differentiation of essential tremor, psycho-
genic parkinsonism, orin
neuroleptic
induced
Amyloid
the
Brain
Pathologic
Basis of
Inflammation
parkinsonism from presynaptic parkinsonian
Imaging
syndromes (Parkinson’s disease, multiple-
Vulnerable
plaques
havedegeneration,
typically large
system atrophy,
corticobasal
progressive
palsy) by thin finecrotic
coressupranuclear
that are covered
brous
caps
(2). ofMany
foamdisease
cells are seen
• Early
detection
Parkinson’s
around
the
necrotic
cores.
There
is exten• Assessment of disease severity and progression
sive
inflammation
within
the
fibrous
• Differentiation of dementia with Lewy bodiescaps;
the more
macrophages,
from other
dementias the thinner the cap.
Migration of monocytes to the subintimal
layers of the plaque is associated with deContinued on
2. See DaT Imaging
velopment of receptors
forpage
chemoattractant
factors, such as monocyte chemotactic protein-1 (MCP-1); adhesion molecules, such as
vascular cell adhesion molecule-1 (VCAM-1)
(1); and expression of scavenger receptors,
including SRAI/II, CD68 and FcRIII.
Times
Square Jumbotron
In addition to
upregulation
of various 3surface receptors, foam cells in the neointima
SNM andsuch
AACRas inter4
release numerous cytokines,
leukin-1, tumor necrosis factor-� and MCPMI References
4
1 (3). Activated macrophages
also release
metalloproteinases and other proteolytic
Meetings & Awards
5 to
enzymes, suchCMIIT
as cathepsins,
which lead
degradation of the matrix, thinning of the fiSNM outward
Name Change
5
brous cap and positive
remodeling
of the vessel wall. Cell death is commonly obTech Corner 6
IN THIS ISSUE
Continued on page 2. See Plaque.
MI in the News
7
DaT Imaging. Continued from page 1.
Figure 3: 123I-ioflupane images: normal subject and various stages of Parkinson’s
disease
Figure 1: 123I-ioflupane structure
Anti-parkinsonian medications usually do not significantly
interfere and therefore do not need to be discontinued. Of course,
cocaine and related substances, such as methylphenidate, fentanyl, or ketamine, may interfere with DaT binding and should
be discontinued (see Booij et al. Eur J Nucl Med Mol Imaging
2008;35:424-38 for an extensive list of interfering medications).
Three to six hours after injection, SPECT images are acquired on
a dual (or more) head gamma camera. On a dual head camera,
this typically takes 30-45 minutes. A detailed procedure guideline
is downloadable from the Society of Nuclear Medicine Web site
(“Practice Management”>“Procedure Guidelines”>“Neurology”).
Image Interpretation
2
Figure 2: Dopaminergic synapse in the striatum
respond better to therapy with acetylcholinesterase inhibitors but
may suffer severe side effects if given neuroleptic drugs and have
worse prognosis. In DLB, DaT binding is reduced, whereas in most
other dementias (with the exception of dementia associated with
PD), DaT binding is normal.
Technical Aspects
Typically 185 MBq (5 mCi) of 123I-ioflupane is injected intravenously. To reduce exposure of the thyroid to free 123I, the thyroid
can be blocked at least one hour before tracer injection, although
even without blocking, the radiation dose to the thyroid would
be low. The only contraindications are pregnancy, the inability to
cooperate with SPECT brain imaging, or a known hypersensitivity
to the active substance or to any of its excipients (which is rare).
Iodine allergy is not a contraindication. Breastfeeding should be
interrupted for at least 24 hours after injection.
www.snm.org/cmiit mi
Images should be reoriented to a standard plane to avoid the
false appearance of asymmetry due to head tilt. Images should be
checked for asymmetry and a decrease of the target to background
ratio. In a normal scan, the striatum is clearly visible as right and
left symmetric, comma-shaped regions, with both caudate and putamen showing a high intensity compared to background (Figure
3). With increasing age, a slight decline in target to background
ratio is expected (typically some 5-8 percent per decade).
In early PD there is usually an asymmetrical pattern of reduced DaT binding starting in the dorsal putamen contralateral to
the clinically most symptomatic body side, gradually progressing
anteriorly and ipsilaterally as the disease becomes more severe.
Activity in the caudate nucleus is relatively preserved in early disease but will also decline with advancing disease. In the atypical
parkinsonian syndromes (MSA, PSP), there usually will be a more
symmetrical decrease in DaT binding and relatively more involvement of the caudate nucleus; however, there is too much overlap
to reliably differentiate between PD and these other conditions. In
DLB, DaT binding is reduced, typically with bilateral loss of DaT
binding, mainly in the putamen but also in the caudate and generally with less asymmetry than in PD.
Many specialized centers also use semiquantitative image assessment in which specific binding ratios are calculated, e.g., the
ratio of striatal to occipital activity. These can be compared to values of a normal reference population. Because semiquantification
is influenced by many factors (e.g., camera, scanning protocol, reconstruction algorithms, semiquantification method, etc.) there is
no universal cutoff value for normal vs. abnormal. Each site needs
to establish its own normal reference range. Although semiquantification may have some advantages, especially for research purposes or in case of very subtle changes, it usually is not necessary
Continued on page 3. See DaT Imaging.
See DaT Imaging. Continued from page 2.
because the decrease in DaT binding is clearly visible even in the
early stages of disease.
syndromes. 123I-ioflupane SPECT can also be used to differentiate
dementia with Lewy bodies from other types of dementia, such as
Alzheimer’s disease.
Conclusion
Marcel Janssen, MD, PhD, is a nuclear medicine physician in
the Department of Nuclear Medicine of the Radboud
University Nijmegen Medical Centre, Nijmegen, The
Netherlands.
Dopamine transporter imaging with 123I-ioflupane has recently been FDA approved. It is a robust and simple technique
that can sensitively detect or rule out degeneration of presynaptic
striatal dopaminergic nerve cells. It can differentiate presynaptic
parkinsonian syndromes (PD, MSA, PSP) from essential tremor,
drug-induced parkinsonism and psychogenic parkinsonism, but
it cannot differentiate between these presynaptic parkinsonian
MI Training. Continued from page 1.
curricula and a white paper on molecular imaging training for scientists was published. The task force submitted formal suggestions
to the Residency Review Committee in both 2007 and 2008 for
the expansion of the nuclear medicine residency curriculum that
included increased emphasis on 13 “advanced practice” topics. Although these suggestions have not yet been incorporated in the
residency curriculum, SNM is now offering a training course on
this material.
A new series of educational lectures in molecular imaging
debuts in 2012 in a monthly webinar format. The curriculum is
designed primarily for nuclear medicine and radiology residents
in order to provide a firm foundation in the basic principles of
molecular imaging. The course is primarily designed for nuclear
medicine and radiology residents, but is also helpful for physicians, scientists, technologists and other professionals who want
a better understanding of molecular imaging. This series of webinars is designed to educate participants on the basic principles of
molecular imaging, including methods employing radioisotopes,
optical imaging agents and magnetic resonance.
At the conclusion of the program, participants will be able to:
•
Review the basic science of molecular imaging, including
molecular and cellular chemistry, biochemistry, biology,
imaging physics and instrumentation.
• Apply key concepts to effectively communicate and interact with experts in molecular imaging.
• Discuss the current and future roles of advanced molecular imaging techniques and agents for clinical imaging of
disease.
The following topics will be offered monthly (and on-demand) with CME and VOICE credit: Molecular and Cellular Biology Overview, Cell Trafficking, Animal Imaging and Instrumentation, Magnetic Resonance Imaging and Spectroscopy, Molecular
Imaging of the Heart, Optical Imaging, Techniques and Agents,
Apoptosis, Angiogenesis, Proliferation, Reporter Genes, Amyloid
Imaging, Hypoxia, and Molecular Imaging with
Ultrasound Technology.
Through training mechanisms such as this
course, SNM hopes to help grow and evolve the
field of molecular imaging.
Heather Jacene, MD
SNM Brings Molecular Imaging to the Public on Times
Square Jumbotron
O
n December 23, SNM debuted a 15-second message on the CBS jumbotron
screen in New York City’s Times Square to
raise public awareness of molecular imaging.
The video will run once an hour for three
months, including the holiday season and
the New Year’s Eve celebration, which alone
attracted an estimated one million people.
The CBS “Super Screen” is 26 feet tall
and 20 feet across and is strategically positioned at 42nd St. between 7th and 8th Avenues in the heart of the Times Square Plaza.
It is estimated that 1.6 million people pass
through Times Square each day.
The video focuses on how molecular
imaging can provide earlier diagnosis and
directs people to SNM’s new patient website,
discovermi.org, for more information.
3