Open Journal of Me di cal Imaging, 2011, 1, 15-20
doi:10.4236/ojmi.2011.12003 Published Online December 2011 (
Copyright © 2011 SciRes. OJMI
Fluorine-18 Fluorodeoxyglu cose Positron Emission
Tomography for Osteochondromas Utilizing a
Triple-Time Point Protocol
Chris Sambaziotis1, Andrew Lovy1, Renee M. Moadel2, Murthy Chamarthy2, Joseph Glaser2,
Srividya Jaini2, Esperanza Villanueva-Siles3, David S. Geller1*
1Department of Orthopaedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA
2Department of Nuclear Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New Yor k, USA
3Departmen t o f Pathology , Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA
E-mail: *
Received October 11, 2011; revised December 1, 2011; accepted December 10, 2011
Purpose: The purpose of this study was to assess solitary osteochondroma and hereditary multiple osteo-
chondral exostoses (HMOCE) utilizing FDG PET and a triple time point protocol. Methods: Seven patients
were consented and recruited for PET evaluation of presumed benign osteochondroma. Following injection
of 15 mCi of FDG, the lesion(s) of interest was imaged with PET-CT at 45 minutes post injection, whole
body at 50 minutes post, and lesion of interest at 95 minutes post injection. A maximum standardized up-
take value (SUVmax ) was obtained for the lesion(s) of interest at each time point, and an SUVΔ was calcu-
lated for each lesion of interest from the first time point to the third time point. Results: 16 lesions from 7
patients were included in the study. Mean SUVmax for all 3 time points was 1.04 with a standard deviation
of 0.50 (range 0.3 - 2.2). The mean SUV was 0.096 with a range of 0 - 0.4. Among the 3 patients with his-
tologically confirmed osteochondromas, mean SUVmax was 0.67, with standard deviation of 0.23 and range
of 0.3 to 1.0. The mean SUVΔ13 was 0.081 (range 0 - 0.4), mean SUVΔ12 was 0.10 (0 - 0.3), and mean
SUVΔ23 was 0.11 (range 0 - 0.4) (p = 0.74). Conclusion: Benign lesions were found to not have progres-
sively increasing uptake on multiple time point FDG PET. Until chondrosarcomas are evaluated using tri-
ple time point 18FDG PET, its applicability in the evaluation of osteochondroma versus malignant change
remains uncertain.
Keywords: Positron Emission Tomography, Osteochondroma, Chondrosarcoma, Fluorine-18
1. Introduction
Osteochondromas are the most common benign cartila-
genous tumors, typically presenting during the second
decade and often diagnosed as incidental radiological
findings [1]. Lesions may be solitary or multiple as in
hereditary multiple osteochondral exostoses (HMOCE),
which is an autosomal dominant disorder characterized
by two or more exostoses. The primary concern for pa-
tients with osteochondromas or HMOCE is the risk of
malignant transformation, with described rates of less
than 1% and 5% to 25% respectively [2-4]. Asympto-
matic lesions require observation and can be closely
monitored for signs of malignant change.
The key to surveillance is early detection of malignant
transformation; however this is a daunting task especially
in HMOCE, where multiple lesions limits conventional
imaging modalities and continued growth beyond skele-
tal maturity may occur [5,6]. While several imaging mo-
dalities including radiographs, ultrasound, magnetic re-
sonance imaging (MRI) and computed tomography (CT)
are used for initial evaluation, F18 fluoro-2-deoxy-glu-
cose (18FDG) positron emission tomography (PET) can
provide additional physiologic information. 18FDG shares
an intracellular transport mechanism with glucose, re-
sulting in increased uptake in metabolically active cells
As a result, 18FDG PET has become increasingly re-
lied upon for diagnosis and staging of numerous neoplas-
tic processes including lung, breast, and colon cancer [7].
Several studies have also evaluated the diagnostic value
of PET in a variety of musculoskeletal lesions [3,5,8-10],
and have reportedly distinguished benign from malignant
musculoskeletal lesions with a sensitivity of 90.9% to
91.7% and specificity of 100% in trials involving 29 and
45 patients respectively [11,12]. The diagnostic criteria
of these studies are largely based upon standardized up-
take values (SUV) obtained at a single time point of 60
minutes following injection of 18FDG, despite 18FDG’s
half-life of approximately 110 minutes. Additional stud-
ies have evaluated the use of dual time point 18FDG PET,
noting additional diagnostic accuracy compared to stan-
dard single time point 18FDG PET scanning [13,14]. The
purpose of this study is to assess and describe the inher-
ent characteristics of 18FDG PET utilizing triple time
points in solitary osteochondroma and HMOCE. We
hypothesize that the addition of a third time point will
result in better characterization of osteochondromas
based on the half-life of 18FDG.
2. Methods
Approval was obtained from the Institutional Review
Board prior to beginning of the study. From 2008 to
2010, all patients with suspected or diagnosed osteo-
chondroma or chondrosarcoma, including patients with
recurrence, were eligible for participation in the trial.
Pregnant and/or lactating women, infants and children
under 12 years of age and those subjects who would not
be able to tolerate the exam were excluded from the
study. In addition, diabetic patients were also excluded to
prevent interference with quantitation of FDG metabo-
lism. Patients participating in the study were scheduled
for an FDG PET-CT scan utilizing a triple time point
Following history, physical exam, and conventional
imaging studies such as plain radiographs, MRI or CT,
patients underwent a triple time point FDG PET-CT scan.
Before undergoing FDG PET-CT study, patients were
instructed to fast for 4 hours prior to the scan and blood
sugar levels were checked to ensure fasting levels of
<160 mg/dL. Intravenous access was obtained and 15
mCi of FDG was injected intravenously in standard
fashion. Low dose CT scans were performed using 120
kV and 50 - 100 mAs for adults and 20 - 30 mAs for
children. Field-Of-View (FOV) was 600 mm, with 5 mm
slices acquired in increments of 5. Collimation was
separate on all scanners. Pitch and rotation were 0.813
and 0.5, respectively. Imaging matrix was 512 × 512.
After injection, three PET-CT scans were obtained. The
first scan was a regional scan that started approximately
45 minutes (T1) post injection and proceeded for 5 min-
utes over the tumor(s) of interest. The second scan was a
whole body scan (top of head to toes) and started ap-
proximately 50 minutes (T2) post injection and pro-
ceeded for approximately 30 minutes. The third scan was
a regional scan that started approximately 95 minutes (T3)
post injection and proceeded for 5 minutes over the tu-
mor(s) of interest. All images were acquired using a
Philips GEMINI TF PET-CT system (Netherlands) and
reconstructed utilizing an iterative reconstruction algo-
rithm with low-dose CT attenuation correction. Images
were analyzed on a Philips workstation in the transaxial,
coronal and sagittal planes. A maximum standardized
uptake value (SUVmax) was obtained for the tumor(s) of
interest within the field of view at each time point (SU-
VmaxT1, SUVmaxT2, SUVmaxT3) using the equation be-
SUV = tissue activity (mCi/mg)/[injected FDG dose
(mCi)/body weight (kg)]
Additionally, SUV deltas (SUVΔ12 = SUVma x T1
SUVmaxT2, SUVΔ13 = SUVmaxT1 – SUVmaxT3, SUVΔ23 =
SUVmaxT2 – SUVmaxT3) were calculated for the tumor(s)
of interest. A SUVmax was measured for all other tumors
seen in the whole body scan at T2.
When possible, diagnosis was confirmed histologi-
cally. In the majority of cases osteochondromas exhibit
normal-appearing medullary bone and marrow fat/ele-
ments surrounded peripherally, by a variable thickened
cartilagious cap. The chondrocytes in the cartilage may
be solitary or clustered and may undergo enchondral
ossification resembling the epiphyseal growth plate.
The mean, range and standard deviation of the SUVmax
and SUV measurements were calculated for both osteo-
chondromas and HMOCE lesions, and compared using
Wilcoxon rank sum test, and Kruskal-Wallis test.
3. Results
Seven patients with a total of 16 discrete lesions were
enrolled in the study, of which 3 patients had solitary
osteochondromas and 4 patients had HMOCE (Table 1,
Figure 1). The mean SUVmax from all 3 time points was
1.04 with a standard deviation of 0.50 and range of 0.3 -
2.2 (Table 2). The mean SUVΔ13 was 0.081 with a
range of 0 - 0.4, the mean SUVΔ12 was 0.10 with a range
of 0 - 0.3, and the mean SUVΔ23  was 0.11 with a range
of 0 - 0.4 (p = 0.74). Among patients with HMOCE, 3
patients had 3 lesions and 1 patient had 4 lesions for a
total of 13 lesions in the study. There was no difference
in mean SUVmax among patients with solitary lesions
(0.96 ± 0.12) compared to patients with HMOCE (1.06 ±
0.55) (p = 0.68). The mean SUVΔ among patient with
solitary lesions and HMOCE was 0.022 and 0.11 respec-
Copyright © 2011 SciRes. OJMI
Table 1. Patient demographic characteristics.
Age: yrs 35.1 ± 9.8
Total: n 7
Male: n (%) 4 (57%)
HMOCE: n (%) 4 (57%)
Solitary Osteochondroma: n (%) 3 (43%)
HMOCE = hereditary multiple osteochondral exostoses.
Figure 1. Box plot of SUVmax values by patient.
tively (p = 0.02).
Tumors were histologically confirmed to be benign
in 3 patients who underwent surgical resection secon-
dary to pain (Figures 2 and 3). The mean SUVmax
among patients with confirmed benign lesions was
0.67, with standard deviation of 0.23 and range of 0.3
to 1.0.
Of note, patient 3 had an SUV 2 with a range of 1.6
to 2.2, and there is no histopathological correlation. How-
ever, the patient remained clinically stable during 2-years
4. Discussion
While advanced or large malignancies are readily identi-
fied using conventional radiographic methods, the early
detection of malignant transformation of osteochondro-
mas remains a clinical dilemma. Although historically a
cartilage cap of >1 cm was thought to indicate malignant
potential, large benign caps have been described particu-
larly in patients with HMOCE whose lesions may con-
tinue to grow beyond skeletal maturity. Bone scans are
nonspecific and their ability to distinguish malignant
from benign entities is poor. Previous studies have
evaluated the diagnostic utility of positron emission to-
mography in musculoskeletal lesions, as well as in lung,
breast, and colon cancer [3,5,7-10]. These studies sug-
gested malignant transformation with maximal standard-
ized uptake values greater than 2.0 or 3.0, while more
recent studies noted improved diagnostic accuracy util-
Table 2. SUVmax values by timepoint & SUV.
Time Lesion 1 Lesion 2 Lesion 3Lesion 4
T1 1 0.6 1.1 0.8
T2 0.9 0.6 1 0.8
T3 0.9 0.6 1 0.7
Patient 1
SUVΔ13 0.1 0 0.1 0.1
T1 1 0.9 1.2
T2 0.9 1 1
T3 1 0.9 1.2
Patient 2
SUVΔ13 0 0 0
T1 2.1 1.9 1.8
T2 2.1 2.2 1.6
T3 2 1.9 2
Patient 3
SUVΔ13 0.1 0 0.2
T1 0.6 0.7 0.5
T2 0.7 0.5 0.4
T3 0.5 0.3 0.4
Patient 4*
SUVΔ13 0.1 0.4 0.1
T1 0.8
T2 0.8
T3 0.8
Patient 5*
SUVΔ13 0
T1 1
T2 1
T3 1
Patient 6*
SUVΔ13 0
T1 1
T2 1.1
T3 1.1
Patient 7
SUVΔ13 0.1
*Tumors were histologically confirmed to be benign. Only the SUVΔ13 is
listed for each lesion due to the non-significant difference between the
SUVΔ13 values.
izing dual time point PET scans compared to single time
point scanning [13,14].
Aoki et al., investigated the results of PET scan be-
tween benign cartilaginous tumors and chondrosarcoma
and found that the average SUVmax for the chondrosar-
coma group to be 2.23 ± 0.80, with a range from 1.3 to
3.3 [8]. Based on these findings, a SUV of 1.3 was sug-
gested as a possible cutoff for differentiating benign
from malignant cartilaginous tumors. Similarly, Feldman
et al. [11] found that an average SUVmax of 2.0 differen-
tiated between benign and malignant lesions with a sen-
Copyright © 2011 SciRes. OJMI
Figure 2. 19-year-old female with solitary right medial tibia
osteochondroma that was surgically resecte d due to pain. (a)
Osteochondroma on hematoxylin and eosin stain (20×)
demonstrating calcification of the cartilage cap, before go-
ing enchondral ossification; (b) PET (first row), CT (second
row) and fused (third row) displayed in the transanxial,
sagittal and coronal planes showing the right medial tibia
osteochondroma (circle) at T2 where SUVmax = 0.8.
sitivity of 91.7% and a specificity of 100%. Additionally,
all aggressive lesions had a SUVmax > 2.0. More recent
literature investigated the mean maximal standard uptake
values in benign cartilaginous tumors, grade-1 chondro-
sarcomas, and high-grade chondrosarcomas [10]. Their
results did not show a significant difference between
benign cartilage tumors (1.147 ± 0.751), and grade-1
chondrosarcomas (0.898 ± 0.908), but did show a sig-
nificant difference between low-grade (benign and gr-
ade-1 chondrosarcoma) and high-grade chondrosarcomas
Figure 3. 25-year-old man with single right medial femur
osteochondroma that was surgically resecte d due to pain. (a)
Osteochondroma on hematoxylin and eosin stain (10×) with
hyaline cartilage cap covered by fibrous perichondrium.
The superficial cancellous bone of the stalk is undergoing
enchondral ossification; (b) PET (first row), CT (second
row) and fused (third row) displayed in the transanxial,
sagittal and coronal planes showing the right medial femur
osteochondroma (circle) at T2 where SUVmax = 1.0.
(6.903 ± 5.581). These results demonstrate the difficulty
and radiological limitations in determining malignant
transformation of benign cartilaginous tumors from
low-grade chondrosarcomas.
The current study demonstrates concordant results
with those previously published in regards to maximum
standardized uptake values in benign osteochondromas.
The previous cutoff of 2.0 is supported in our study when
examining the SUVmax in those with confirmed histologic
benign lesions, with a range from 0.3 to 1.1 (mean 0.67 ±
Copyright © 2011 SciRes. OJMI
0.24). Furthermore, our study demonstrates that benign
lesions do not have progressively increasing uptake on
multiple time point FDG PET unlike metabolically active
malignant lesions as shown in the prior studies. Thus, for
benign osteochondromas, the addition of a triple time
point did not provide additional clinical utility.
The use of imaging modalities such as ultrasound, CT
or MRI to differentiate benign osteochondromas from
secondary chondrosarcomas is well described in the lit-
erature [15-18]. Cartilage cap thickness is commonly
used as a marker of malignant transformation as malig-
nant transformation typically occurs with cartilage cap
thicknesses greater than 1 - 3 cm [15]. In a study of 101
patients, 34 of which had secondary chondrosarcomas,
Bernard et al. [19] suggested a 2 cm cutoff based on their
described imaging technique to distinguish benign os-
teochondromas from secondary chondrosarcomas. The
sensitivity and specificity of a 2 cm cutoff was 100% and
98% for MRI and 100% and 95% for CT, which are en-
couraging results and which arguably may support this
method of evaluation as the current standard of care [19].
Limitations of our study include a small sample size as
well as a lack of malignant tumors for comparison and
characterization. Even though maximum standardized
uptake values utilizing triple time points were similar in
histologically confirmed benign lesions, we were unable
to make a similar conclusion for low or high-grade
chondrosarcomas, which are inherently more metaboli-
cally active. In addition, the natural history of osteo-
chondromas and their malignant transformation rate is
quite rare, making it difficult to evaluate the use of PET
scan to differentiate benign osteochondroma from chon-
drosarcoma at a single institution.
In conclusion, our preliminary study demonstrated that
maximum standardized uptake values utilizing triple
time point FDG PET for histology confirmed osteochon-
dromas showed no difference to previously published
values utilizing single or dual time point protocols. The
clinical utility of triple time point protocol based on the
half-life of FDG in chondrosarcomas, which are inher-
ently more metabolically active, remains unknown. A
multi-institutional study would provide increased num-
bers and the ability to detect the rare transformation of
osteochondromas to chondrosarcomas. This may ulti-
mately enable investigators to determine reliable and
relevant SUV cutoff points allowing for the distinction of
benign osteochondromas from low-grade chondrosarco-
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