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Diagnosing, staging, and re-staging of cancer, as well as the
monitoring and planning of cancer treatments, has traditionally
relied on anatomic imaging with computed tomography (CT) or
magnetic resonance imaging (MRI). These anatomic imaging modalities
provide exquisite anatomic detail and are indispensable
specifically for guiding surgical intervention. However, they are
limited in their ability to characterize masses reliably as
malignant or benign. Necrotic, scar, or inflammatory tissue often
cannot be differentiated from malignancy based on anatomic imaging
In contrast, molecular F-18 deoxyglucose (FDG)-PET imaging
utilizes the markedly increased glucose metabolic activity of tumor
cells and provides images of the whole body distribution of
phosphorylated FDG. Increased glucose utilization and, thus,
increased uptake of FDG in tumor cells is facilitated by: 1)
increased activity of cell membrane glucose transporters, 2)
increased hexokinase activity, and 3) increased rates of the hexose
The fundamental differences between anatomic (i.e., CT and MRI)
and molecular (i.e., PET) imaging can be summarized as follows:
anatomic imaging detects structural abnormalities with a high
accuracy. Size criteria fail to characterize structural
abnormalities reliably as malignant or benign. This implies that
anatomic imaging generally has a high sensitivity for the detection
of structural alterations, but a low specificity for further
characterizing these abnormalities.
THE POWER OF MOLECULAR PET IMAGING
More recently, the medical community has embraced molecular
imaging with PET and the glucose analogue FDG as a means to
discriminate benign from malignant lesions accurately. This is
based on the fact that malignant tissue exhibits markedly increased
rates of glucose consumption. Because cell alterations at the
molecular level precede anatomic tissue alterations, whole-body
imaging with FDG consistently diagnoses, stages, and re-stages
cancer with a substantially higher accuracy than CT. For instance,
Dwamena et al
conducted a meta-analysis to compare the performance of PET and CT
for mediastinal lymph node staging in lung cancer patients. Using
stringent selection criteria, this analysis included 514 lung
cancer patients studied with PET (included in 14 published studies)
and 2226 patients evaluated with CT (derived from 29 studies). They
concluded that PET demonstrated both higher sensitivity (79% versus
60%) and specificity (91% versus 77%) than CT for correctly
classifying mediastinal lymph nodes.
Similar observations have been made in patients with lymphoma,
and many other malignancies. FDG-PET has also been established as a
powerful prognostic tool in cancer patients.
Finally, the effects of various treatments on cancer tissue can be
monitored reliably early after the initiation of treatment.
Gambhir and coworkers
have recently summarized the power of FDG-PET based on tabulated
research data obtained in more than 26,000 patients with a variety
of cancers. PET was 10% to 20% more accurate than conventional
imaging for diagnosing staging and restaging most cancers.
Based on this body of evidence, Medicare is now covering PET for
diagnosis, staging, and restaging of lung cancer, colorectal
cancer, lymphoma, melanoma, head and neck cancer, and esophageal
cancer. CMS recently has also approved FDG-PET for restaging and
monitoring the treatment of patients with breast cancer.
While molecular PET imaging evaluates cancer patients more
accurately than anatomic imaging, several issues remain unresolved.
First, PET using FDG or more specific tracers does not provide
exact localization of molecular abnormalities. Thus, additional
anatomic imaging for localizing abnormalities is necessary in many
patients. Secondly, clinical whole-body PET studies are relatively
time-consuming, requiring 45 to 60 minutes of imaging time.
MOLECULAR AND ANATOMIC IMAGING
Several studies have shown that PET and CT, when evaluated
together, increased the accuracy of both tests. Chin et al
reported a series of 30 patients studied with PET and CT to
determine mediastinal lymph node involvement. They concluded that
the combined information of PET and CT yielded the highest
diagnostic accuracy (90%). Similarly, Weng et al
also reported a higher diagnostic accuracy for PET and CT than for
PET or CT alone for lung cancer staging. Magnani et al
reported that 25 of 28 patients were staged correctly with PET+CT,
while only 21 and 22 patients, respectively,, were staged correctly
with CT or PET alone.
Vansteenkiste et al
compared the accuracy of visually analyzed FDG-PET and CT images
with that of CT alone for the mediastinal staging of 68 lung cancer
patients. State-of-the-art spiral CT and a dedicated whole-body PET
scanner were used. Invasive surgical staging was used as the gold
standard in all patients for a total of 690 lymph node stations.
Overall, the diagnostic accuracy was better for PET+CT than for CT
alone (87% versus 59%). PET+CT was also superior to CT alone for
detecting locally advanced disease (N2/N3). Sensitivity,
specificity, and accuracy of CT alone were 75%, 63%, and 68%
compared with 93%, 95%, and 94% for PET+CT (
= 0.0004). Based on their findings of a very high negative
predictive value of PET, these authors reported that
mediastinoscopy could have been omitted in 29 of 68 patients.
DUAL-MODALITY PET/CT IMAGING
Analysis of retrospectively aligned PET and CT images is,
however, error-prone, time-consuming, and tedious. Moreover, true
image fusion is difficult given the different patient positioning
between the PET and the CT scan.
To avert these problems, a team at the University of Pittsburgh
headed by Drs. David Townsend in collaboration with CTI Molecular
Imaging, Inc.(Knoxville, TN) and Siemens Medical Solutions (Hoffman
Estates, IL) developed a dual-modality PET/CT tomograph combining
both PET and CT scanning in one device.
This first prototype to be used clinically consisted of a rotating
partial-ring PET system and single-slice CT scanner mounted to the
same rotating support. Since the introduction of this prototype,
several PET/CT devices have been introduced and are now available
commercially (CTI Molecular Imaging, Inc.; GE Medical Systems,
Waukesha, WA; Philips Medical Systems, Bothell, WA; Siemens Medical
Solutions). As of the time of this writing, nedarly 100 PET/CT
scanners have been installed worldwide.
INITIAL RESEARCH EXPERIENCE WITH PET/CT IMAGING
The first clinical studies investigating the advantages of
PET/CT over PET or CT imaging alone have been published. Martinelli
reviewed more than 100 oncology studies acquired with the prototype
PET/CT scanner at the University of Pittsburgh. From their
observations in patients with a variety of malignancies, they
concluded that PET/CT offered significant advantages including more
accurate localization of FDG-uptake, distinction of pathological
from physiologic uptake, and improvements in monitoring
The same group also investigated in a small case series the
impact of the PET/CT on patient management.
Management changes included, for instance, modifications of
surgical or medical approaches.
As mentioned above, PET/CT should prove especially useful for
evaluating "difficult-to-image" regions of the body. These include
the head and neck, the mediastinum, and the postsurgical abdomen.
Kamel and co-workers
from the University Hospital of Zurich reported focal FDG uptake in
the lower anterior neck in 6 of 184 patients who underwent lung
cancer staging. Using the PET/CT device revealed that the FDG
uptake was localized in hypertrophied normal laryngeal muscle
caused by contralateral laryngeal nerve tumor invasion. Obviously,
the PET/CT assessment avoided the false positive findings of PET
Makhija et al
used PET/CT to evaluate patients with suspected recurrent ovarian
cancer. PET/CT identified the site of recurrence in 5 (62%) of 8
patients who had negative CT findings.
Published evidence on the merits of PET/CT for evaluating cancer
patients is currently evolving. This is because the technology is
new and initial clinical evaluations of PET/CT imaging have not
been finalized. However, during the 2002 meeting of the American
Society of Nuclear Medicine more than 50 abstracts addressed the
role of PET/CT imaging. Several of these scientific papers shed
light on the merits of PET/CT imaging.
Cohade and co-workers
evaluated in 358 patients the supraclavicular "muscle-uptake" PET
artifact using PET/CT. They found in a significant portion that
this artifact might be caused by "brown" fat and not by increased
glucose metabolic rates of striated muscle.
Equivocal PET lesions were also evaluated with PET/CT by Yeung
Analyzing the findings in the first 100 patients studied with
PET/CT, they reported that 57% of the equivocal PET findings could
be classified correctly into normal or abnormal categories. Thus,
PET/CT aids in differentiating benign or artifactual lesions from
The role of PET/CT for evaluating patients for lung cancer
recurrence was assessed by Keidar et al.
This study of 26 patients revealed that PET/CT provided important
additional information in 56% of the patients. The added value of
PET was related to improved lesion localization and differentiation
between physiological and pathological FDG uptake. Importantly,
lesions missed by CT initially were visualized by PET/CT and were
identified subsequently on CT images.
Another study examined the added value of PET/CT imaging in
PET/CT improved the accuracy of PET in 48% of the patients mainly
by improving lesion localization, and led to retrospective
detection of CT abnormalities in a considerable number of
The impact of PET/CT imaging on the preoperative staging of lung
cancer patients was evaluated by Steinert et al.
These authors reported an incremental impact of PET/CT imaging with
increasing patient stage. While PET/CT altered the stage in only 1
of 9 patients with stage I or II disease, it impacted stage IIIA in
5 of 6, 6 of 6 patients with stage IIIB, and 8 of 8 patients with
stage IV disease. The authors concluded that PET/CT was superior to
PET or CT alone in initial staging of lung cancer.
Another advantage of PET/CT in the staging/restaging of lung
cancer patients was provided by Osman et al
in 34 patients. These authors reported significantly fewer
"probable" or "equivocal" lesions with PET/CT than with PET alone.
Further, lesion localization was improved significantly by
One important emerging clinical contribution of PET/CT is its
role in the field of radiation oncology, specifically radiation
planning. This is because CT alone can only delineate mass lesions,
but frequently fails to determine reliably the amount and extent of
viable tumor. Dizendorf et al
evaluated prospectively the impact of PET/CT on radiation planning
in 30 consecutive patients scheduled to undergo external beam
radiation. CT determined the target volume of PET/CT. Combined
PET/CT changed the radiation treatment strategy from curative to
palliative in 20% of the patients. In 30% of the patients, the
radiation dose was changed and changes of the target volume were
reported in 40% of the patients. The impact of these modifications
on patient outcomes will need to be addressed in future
Several technical limitations of PET/CT need to be addressed.
Foremost among these are artifacts induced by patient or
or artifacts from dental metallic implants.
For instance, respiratory or patient motion induces artifacts on CT
and thus, PET/CT images.
Goerres and co-workers attempted to optimize respiration during the
CT portion of the study. They concluded from their study in 28
cancer patients that a normal expiration protocol during CT
provides the best image co-registration. The authors further
stated, "that a perfect match between PET and CT is not possible,
but the attainable quality of image co-registration is in the range
of the resolution of the PET camera."
Limitations of PET/CT imaging were discussed by Osman et al.
These authors analyzed the frequency of inaccurate lesion
localization with PET/CT. Such incorrect localization induced by
respiratory or patient motion occurred in 6 of 285 patients and was
most frequently explained by mislocalization of liver lesions into
the base of the right lung.
The same group evaluated the influence of metallic dental work
on the quality of PET images.
The authors reported artifacts on both PET images corrected with CT
data and those corrected for photon attenuation using a
conventional 68Ge transmission source. They concluded from their
findings that non-attenuation corrected PET images should be
reviewed in these patients in order to avoid this artifact.
CURRENT PET/CT IMAGING PROTOCOLS
The standard patient preparation employed for PET and CT studies
is applied to the PET/CT device. Patients receive 370 to 550 MBq of
FDG 45 to 60 minutes prior to the start of the image acquisition.
After the patient is positioned on the scanner, an initial topogram
is acquired. The topogram is used subsequently to define the
examination range for the PET/CT image acquisition. The spiral CT
scan is performed next, regardless of the use of intravenous or
oral contrast. After completion of the CT portion, the scanner bed
is moved to the starting position and the emission scan is started.
The emission scan duration and bed position varies with the
detector technology used. With conventional bismuth germanate
oxy-ortho silicate (BGO) system, acquisition times will range from
4 to 6 minutes per bed position. The new lutetium
oxy-ortho-silicate (LSO) technology reduces emission scans to 2 to
3 minutes per bed position.
The CT data are used to perform attenuation correction. Image
reconstruction is completed a few minutes after the PET image
acquisition is completed. Because the CT data are used for
attenuation correction, the actual scan duration of a PET/CT
protocol is shorter than that required for a dedicated PET
PET/CT technology is advancing at a breath-taking pace. The
demands for devices consisting of "state-of-the-art" PET and CT
systems that allow for high patient throughput need to be met.
Among the most exciting developments is the introduction of the LSO
detector technology into PET/CT. LSO has a higher light output than
the conventional BGO detectors and a shorter scintillation decay
time resulting in markedly improved count rate capabilities while
the physical detector properties of BGO are maintained. Thus, high
FDG doses can be injected and images can be acquired in the
three-dimensional mode resulting in improved resolution. This
allows for the completion of whole-body PET/CT studies in ¾15
minutes (Figures 1, 2, and 3).
PET/CT devices have been introduced to the clinic and are now
available commercially. This new technology has generated enormous
interest within the medical community. Radiologists and nuclear
medicine specialists worldwide have embraced the concept of merging
molecular with anatomic imaging.
The power of molecular imaging, together with the detailed
anatomic landmarks provided by CT, will dramatically change
diagnosing, staging and restaging of cancer patients; selection of
treatment modalities; planning of radiation therapy; and the
monitoring of surgical, medical, and radiation treatments. Thus,
PET/CT imaging is changing the care of cancer patients in several
a) Metabolic and anatomic whole-body staging of patients can be
performed in one examination and much reduced scan times, thus,
increasing patient comfort.
b) Because of limited patient motion, near ideal fusion of
metabolic and anatomic images can be achieved.
c) Anatomic landmarks provided by CT will greatly facilitate the
assignment of functional abnormalities to anatomic structures.
d) "Difficult to image" regions of the body (such as the head
and neck, mediastinum, and postsurgical abdomen) will be evaluated
with a high diagnostic accuracy.
e) Fused images can be used to target radiation treatment more
accurately and monitor the effects of chemotherapy, surgery, and
The Institute for Advanced Medical Education designates this
continuing medical education activity for 1 hour in Category 1 of
the Physician's Recognition Award of the American Medical
This CME article consists of text and related images appearing
in this newsletter article. You should read the article and
accompanying images in the PDF file, refer to the references, and
complete the self-evaluation quiz available online in order to be
awarded CME credits.
To go directly to the quiz please
Estimated time for completion: One hour
Date of release: November 2005
Expiration date: November 2007
Dr. Czernin is the Director of Nuclear Medicine and an Associate
Professor in the Department of Molecular and Medical Pharmacology,
the Deptartment of Nuclear Medicine, and the Department of
Medicine, University of California, Los Angeles School of Medicine,
Los Angeles, CA.
In compliance with the Essentials and Standards of the ACCME,
the author of this CME tutorial is required to disclose any
significant financial or other relationships he may have with the
manufacturer(s) of any commercial product(s) or provider(s) of any
commercial service(s) discussed in this program.
Dr. Czernin has disclosed that he has a relationship with CPS
Innovations through his participation as board member.
Category 1 CME
This activity has been planned and implemented in accordance
with the Essential Areas and Policies of the Accreditation Council
for Continuing Medical Education through the joint sponsorship of
ArcMesa Educators and Anderson Publishing, Ltd. ArcMesa Educators
is accredited by the ACCME to provide continuing medical education
ArcMesa Educators designates this educational activity for a
maximum of 1 category 1 credit toward the AMA Physician's
Recognition Award. Each physician should claim only those credits
that he/she actually spent in the activity.
After completing this program, the reader will:
* Understand the differences in information provided by
molecular positron emission tomography (PET) and conventional
anatomical computed tomographic (CT) imaging.
* Understand the concept of dual-modality imaging with
* Understand the advantages of PET/CT imaging over PET or CT
Medicare Reimbursement for PET Imaging
Breast Cancer *NEW*
G0252 PET imaging for initial diagnosis of breast cancer and/or
surgical planning for breast cancer (e.g., initial staging of
axillary lymph nodes), not covererd by Medicare
G0253 PET imaging for breast cancer, staging/restaging of local
regional recurrence or distant metastases, i.e., Staging/restaging
after or prior to course of treatment
G0254 PET imaging for breast cancer, evaluation of response to
treatment, performed during course of treatment
G0210 PET Imaging whole body; diagnosis; lung cancer, non-small
G0211 PET Imaging whole body; initial staging; lung cancer;
non-small cell (replaces G0126)
G0212 PET Imaging whole body; restaging; lung cancer;
non-small-cell colorectal cancer
G0213 PET Imaging whole body; diagnosis; colorectal cancer
G0214 PET Imaging whole body; initial staging; colorectal
G0215 PET Imaging whole body; restaging; colorectal cancer
G0216 PET Imaging whole body; diagnosis; melanoma
G0217 PET Imaging whole body; initial staging; melanoma
G0218 PET Imaging whole body; restaging; melanoma
G0219 PET Imaging whole body; melanoma for non-covered
indications (no payment)
G0220 PET Imaging whole body; diagnosis; lymphoma
G0221 PET Imaging whole body; initial staging; lymphoma
G0222 PET Imaging whole body; restaging; lymphoma
Head and Neck Cancer
G0223 PET Imaging whole body or regional; diagnosis; head and
neck cancer; excluding thyroid and CNS cancers
G0224 PET Imaging whole body or regional; initial staging; head
and neck cancer; excluding thyroid and CNS cancers
G0225 PET Imaging whole body or regional; restaging; head and
neck cancer, excluding thyroid and CNS cancers
G0226 PET Imaging whole body; diagnosis; esophageal cancer
G0227 PET Imaging whole body; initial staging; esophageal
G0228 PET Imaging whole body; restaging; esophageal cancer
G0229 PET Imaging; Metabolic brain imaging for pre-surgical
evaluation of refractory seizures solitary pulmonary nodule
G0125 PET Imaging whole body or regional single pulmonary
G0230 PET Imaging; Metabolic assessment for myocardial viability
following inconclusive SPECT study
78459 Heart Muscle imaging determination of myocardial viability
as primary or initial diagnosis prior to revascularization
Above Information abtained from www.CMS.gov
Applications in PET
is published by Anderson Publishing, Ltd., 1301 West Park Ave.,
Ocean, NJ 07712; (732) 695-0600. O. Oliver Anderson, Publisher,
Elizabeth A. McDonald, Managing Editor; Karen King, Art
Sponsored by a grant from CTI Molecular Imaging, Inc. The views
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and do not necessarily reflect those of the publisher or sponsor.
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2002 Anderson Publishing, Ltd.