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Skeletal Scintigraphy With 18F Sodium
Fluoride Positron Emission Tomography (18F-fluoride PET) Offers Greater
Overall Accuracy Than 99mTechnetium-MDP for Prostate Cancer Patients
(January 2008)
For years and years
bone imaging with 99m-Technetium-methylene diphosphate (99mTc-MDP),
which in clinical practice is conventionally referred to as "the bone
scan", has served as the gold standard for evaluation for metastatic
lesions to bone. Scanning with 99mTc was widely recognized as an
imperfect guide, with about only 1% of patients with a PSA value of <20
ng/mL testing positive despite the potential of their harboring
micrometastatic disease. (It can be argued that for patients at
high-risk for metastatic spread the threshold for efficient utilization
of BS may be a lower PSA value of (say) >10 ng/mL.) The superior
specificity and accuracy of the newer technology, i.e. the 18F-fluoride
PET, is gradually changing the venerable paradigm, although orders for
the traditional 99mTc-MDP bone scan may continue due to a lack of
availability of the PET scanners or unfavorable logistics for obtaining
the isotope, lack of awareness of the PET advantage, or just a lingering
emotional attachment to what has become so familiar.
An excellent review
comparing the 18F-fluoride PET with other imaging modalities is
"Skeletal PET with 18F-Fluoride: Applying New Technology to an Old
Tracer", Journal of Nuclear Medicine, January 2008, by Grant FD et al.
writing for a consortium from Children's Hospital, Boston, and from
Harvard and the University of Pennsylvania medical schools. (Per my
request, this article was brought to my attention by Dr. David Djang,
Seattle Nuclear Medicine, whose comments were very helpful in the
construction of the article.)
The biologic mechanism
underlying imaging by both tracers is similar: identification of
increased osteoblastic bone turnover resulting from bone remodeling
stimulated by tumor/microenvironment interactions. The 18F-fluoride is
incorporated into bone as fluoroapatite. After the scan - uniquely - the
18F-fluoride decays into normal hydroxyapatite, leaving no trace of
radioactivity. The uptake of 18F-fluoride into the bone is high and
rapid and then cleared quickly providing the high bone-to-background
ratio that underlies the high spacial resolution/localization
characteristics of this tracer. As a result the time to imaging for
18F-fluoride PET scan is about 1-1.5 hours compared to a wait of about
3-4 hours for 99mTc-MDP. The tomographic imaging of the PET provides a
lesion resolution of between 4-5 mm as opposed to a resolution of 9-12
mm for the 99mTc-MDP planar presentation. The PET technology offers
higher sensitivity and specificity compared to the gamma camera imaging
with 99mTc.
In addition to the
finer spacial resolution, Dr. Djang explained that the superior
localization of PET was the key advantage. Examples: localization of
uptake in facet joints occasions much less worry than pedicle uptake;
increased activity along an end-plate, possibly emanating from an
osteophyte, is of much less concern than a round lesion in a
mid-vertebral body. This confidence of localization is not possible with
planar 99mTc imaging, which is basically a two dimensional photograph,
like a chest X-ray. The 18F-fluoride PET is tomographic, a
three-dimensional study like a chest CT - a true upgrade in technology.
It is possible to perform tomographic imaging with 99mTc ("SPECT") but
the spacial resolution is still inferior, and perhaps more importantly,
a patient would have to lie on the table for 4-5 hours to complete a
single whole body scan - untenable for most patients.
Grant et al.
extensively reviewed studies comparing the 18F-fluoride PET to 99mTc-MDP
in a variety of tumors and the 18F-fluoride PET study consistently found
more lesions. One study compared the total lesions found on 18F-fluoride
PET to the those visualized by the 99mTc-MDP, which showed only 40% of
spinal lesions and 82% of lesions in the appendicular skeleton that were
seen on PET. The authors' conclusion: "These studies have demonstrated
that 18F-fluoride PET is more accurate than planar imaging or SPECT with
99mTc-MDP for localizing and characterizing both malignant and benign
lesions."
Even-Sapir et al., Tel
Aviv, in J Nucl Med, 2006, February, reported a study of 44 patients,
"The detection of bone metastases in patients with high-risk prostate
cancer: 99mTc-MDP planar bone scintigraphy, single- and
multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT."
"In patient-based analysis 23 patients had skeletal metastatic spread
(52%)..."
In their hands the
PET/CT was "more specific than the 18F-fluoride PET alone and more
sensitive and specific than planar and SPECT BS." "Categorizing
equivocal and malignant interpretation as suggestive of malignancy the
sensitivity and specificity of 18F-fluoride PET alone were 100% and 62%
versus 100% and 100% for PET/CT. The negative predictive value for both
scans was 100%.
[The half dozen years
of physician experience with the 18F-fluoride PET at Seattle Nuclear
Medicine has provided sufficient experience in interpretation so that,
for them, the added expense of the hybrid PET/CT is usually
unnecessary].
BOTTOM LINE:
The most accurate and informative assessment of the skeleton for
metastases is critical for appropriate clinical management, especially
at initial presentation for patients with higher risk prostate cancer
where evidence of disease spread has the potential of changing an
original plan of management. Currently the 18F-fluoride PET or the
hybrid PET/CT offer the best opportunity for an optimal diagnosis.
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