Functional Images Reflect Aggressiveness ofEndometrial Carcinoma: Estrogen Receptor
Expression Combined with 18F-FDG PET
Tetsuya Tsujikawa1, Yoshio Yoshida2, Takashi Kudo1, Yasushi Kiyono1, Tetsuji Kurokawa2, Masato Kobayashi1,
Tatsuro Tsuchida3, Yasuhisa Fujibayashi1, Fumikazu Kotsuji2, and Hidehiko Okazawa1
1Biomedical Imaging Research Center, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; 2Department of Gynecology,

Faculty of Medical Sciences, University of Fukui, Fukui, Japan; and 3Department of Radiology, Faculty of Medical Sciences,
University of Fukui, Fukui, JapanThe grade of histologic differentiation is one of the most important prognostic factors in patients with endometrial carcinoma
and postoperative staging. The aim of this study was to investigate whether 16a-18F-fluoro-17b-estradiol (18F-FES) and
18F-FDG PET reflect clinicopathologic features in patients withendometrial tumors. Methods: A total of 22 patients with endometrial adenocarcinoma and 9 with endometrial hyperplasia(mean age, 56.0 6 15.3 y) underwent 18F-FES PET for estrogen
receptor imaging and 18F-FDG PET. Regional values of tracer uptake were evaluated using standardized uptake value (SUV) andthe SUV ratio of 18F-FDG to 18F-FES. The accuracy for predicting
tumor aggressiveness defined as high-risk carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage $Ic or histologic grade $ 2), low-risk carcinoma (FIGO stage #Ib and grade 1), and hyperplasia was compared for each PET parameter using receiver-operating-characteristic (ROC) analysis.
The diagnostic accuracy of MRI findings for clinical staging
was also compared. Results: Although the SUV for 18F-FDG
was significantly lower in endometrial hyperplasia than in carcinoma, a significant difference between high-risk and low-risk
carcinoma was observed only in SUV for 18F-FES. High-risk carcinoma showed a significantly greater 18F-FDG–to–18F-FES ratio(3.6 6 2.1) than did low-risk carcinoma (1.3 6 0.5, P , 0.01) andhyperplasia (0.3 6 0.1, P , 0.005). Low-risk carcinoma showed asignificantly higher 18F-FDG–to–18F-FES ratio than hyperplasia(P , 0.0001). In ROC analysis, the most accurate diagnostic
PET parameter for predicting high-risk and low-risk carcinoma
was the 18F-FDG–to–18F-FES ratio. The optimal 18F-FDG/18FFES cutoff value of 2.0, determined by ROC analysis, revealed
73% sensitivity, 100% specificity, and 86% accuracy, which
was better than the 77% accuracy for MRI. The 18F-FDG–
to–18F-FES ratio of 0.5 yielded a correct diagnosis for carcinoma
from hyperplasia with 100% accuracy. Conclusion: Endometrial
carcinoma reduces estrogen dependency with accelerated glucose metabolism as it progresses to a higher stage or grade.
18F-FES and 18F-FDG PET studies provide a new index of the
18F-FDG–to–18F-FES ratio, which is considered the most informative index reflecting tumor aggressiveness. This index will
Received Nov. 14, 2008; revision accepted Jan. 16, 2009.
For correspondence or reprints contact: Hidehiko Okazawa,
Biomedical Imaging Research Center, University of Fukui, 23-3
Matsuoka-Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
E-mail: okazawa@u-fukui.ac.jp
COPYRIGHT ª 2009 by the Society of Nuclear Medicine, Inc.

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be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial carcinoma.
Key Words: estrogen receptor; endometrial carcinoma; PET;
glucose metabolism; tumor aggressiveness
J Nucl Med 2009; 50:1598–1604
DOI: 10.2967/jnumed.108.060145

E

ndometrial carcinoma is a highly prevalent gynecologic malignancy and one of the most common female
malignant tumors in Western countries, including theUnited States, and in Japan (1,2). Early-stage endometrial
carcinoma shows a good prognosis, and the 5-y survival
rate is reported to be more than 90% in patients with stage
Ia or Ib determined by the International Federation of
Gynecology and Obstetrics (FIGO) classifications (3–5).
On the other hand, patients with advanced disease have asignificantly worse survival. Up to 20% of those withendometrial carcinoma relapse and eventually die of theirdisease. Previous studies suggested that the most important
prognostic factors in endometrial carcinoma were thesurgical FIGO stage, myometrial invasion, histologic type,and differentiation grade (6–10). A noninvasive diagnostic
method to evaluate tumor aggressiveness and pathologic
features would be useful for deciding the therapeuticstrategy and predicting prognosis in patients with endometrial carcinoma.
We previously reported that estrogen receptor (ER)expression coupled with glucose metabolism using
16a-18F-fluoro-17b-estradiol (FES) and 18F-FDG PET isuseful for the differential diagnosis of benign and malignant uterine tumors (11). ER expression and glucose metabolism of uterine tumors showed opposite tendencies(i.e., high glucose metabolism and low ER expression inmalignant tumors and low glucose metabolism and high ER
expression in benign tumors). The purpose of the present
study was to investigate whether regional accumulation of

THE JOURNAL OF NUCLEAR MEDICINE • Vol. 50 • No. 10 • October 2009

18F-FES and 18F-FDG and the uptake ratio of 18F-FDG to
18F-FES correlate with the aggressiveness of endometrial

tumors in terms of stage and pathologic findings.
MATERIALS AND METHODSPatients
Thirty-one patients (mean age, 56.0 6 15.3 y) with endometrial
thickening or suspected malignant tumors at cytologic analysis,
ultrasonography, or MRI participated in this study. None of thepatients received any biopsy or treatment before PET and MRI
studies. Definitive diagnosis was determined by postoperative
histopathologic analysis (n 5 25) or whole-endometrium curettage (n 5 6). Final diagnoses were endometrial adenocarcinoma(n 5 22) and hyperplasia (n 5 9) (Table 1). All 6 cases determinedby whole-endometrium curettage were endometrial hyperplasia. In
surgically staged patients, the final stage and grade were decided
by findings at hysterectomy. The staging, histology, and grading
criteria were based on the 1988 FIGO staging classification (3).
The results for 9 patients with endometrial carcinoma and 4
patients with hyperplasia were previously reported in our recent
study (11). This study was approved by the institutional review
board of the University of Fukui Hospital. Written informed
consent was obtained from all patients studied.
PET Procedures
All patients underwent preoperative PET scans with 18F-FES
and 18F-FDG to compare differences in tracer accumulation. Twoscans were obtained on 2 separate days within 1 wk in random
sequence. We used a whole-body tomograph (Advance; GE
Healthcare) that permits the simultaneous acquisition of 35 image

TABLE 1. Patient Characteristics
Characteristic
Total patients (n)Mean age (y)Age range (y)Menopausal status (n)Premenopausal
Postmenopausal
Histopathologic type (n)Endometrial adenocarcinoma
Endometrial hyperplasia
Stage of carcinoma (n)Ia or Ib
Ic
II
III
Differentiation grade (n)G1G2G3Tumor size (n),1 cm
1–2 cm2 cm ,
High-risk carcinoma (n)Low-risk carcinoma (n)

Value
31
56 6 15
30–84
13
18
22
9
14
3
2
3
12
9
1
14
8
9
11
11

Carcinoma of stage Ib or lower with grade G2 or G3 wasincluded in high-risk group.

slices in a 2-dimensional acquisition mode, with interslice spacingof 4.25 mm. Performance tests showed the intrinsic resolution of
the scanner to be 4.0–5.3 mm in the axial direction and 4.6–5.7
mm in the transaxial direction.
18F-FES was synthesized using a method reported elsewhere(12,13). The specific activity was 100–200 GBq/mmol, andradiochemical purity was greater than 99%. For each 18F-FES
and 18F-FDG PET study, approximately 185 MBq of tracer wereadministered via the antecubital vein. Before the tracer administration of each study, patients fasted at least 4 h to avoid elevationof blood sugar levels in 18F-FDG PET and to reduce tracer
excretion to the intestines in 18F-FES PET. Fifty minutes after
the tracer injection, the patient was positioned supine in the PET
scanner, and a 16-min emission scan was started, with 3-min scansat the pelvic region (2 bed positions) and 2-min scans in eachremaining region (5 bed positions) to completely cover the head to
inguinal regions. Postinjection transmission scans of 2 min at thepelvis and 1 min in other areas were obtained after the emission
scans using a 68Ge/68Ga rod source for attenuation correction. The
PET data were reconstructed by the iterative method, with selection of 14 subsets and 2 iterations. The reconstructed images werethen converted to a semiquantitative image corrected by the
injection dose and the patient’s body weight (standardized uptake
value [SUV]) for data analysis.
MRI Scans and SUV Measurements
All patients underwent MRI during the time between the 2 PET
examinations, or within 1 wk from them, for diagnosis and toobtain anatomic information about the pelvic organs. T1- and T2weighted images in the axial, sagittal, and coronal planes wereacquired with a 1.5-T superconducting MRI system (Signa; GE
Healthcare). The repetition and echo times for T1- and T2weighted images were 533 and 8 ms and 4,700 and 90 ms,
respectively. Contrast-enhanced MRI was performed with orwithout fat saturation in the axial and sagittal planes after the
injection of gadolinium diethylenetriamine pentaacetic acid (0.1mmol/kg). Staging of the tumors based on MRI findings was
performed by board-certified radiologists as follows: intact junctional zone on T2-weighted MR images and superficial myometrial invasion (no more than half) on T2- and contrast T1-weighted
images were regarded as early stages and deep myometrial
invasion (more than half), cervical involvement, and pelvic lymphadenopathy as advanced stages.
Circular regions of interest (ROIs) with a fixed size of 8 mm indiameter were drawn on the lesions to obtain the local SUV.
Individual MR images were referenced for placement of ROIs in
the appropriate region after PET and MR images were coregistered (Body Guide; Advance Biologic Co.). ROIs were placed on
the resliced MRI sections after coregistration of 3 images in eachpatient and the same ROIs were applied to the 18F-FES and 18FFDG PET images. Sagittal or coronal planes (2 or 3) of 6-mm
thickness were used to obtain SUV at the center of the lesion. A
single section at the center of the lesion was used when the lesion
was small and substantial partial-volume effects on the mean SUV
were expected. SUVs for each patient were averaged in 18F-FDG
and 18F-FES PET images. The mean SUV ratio of 18F-FDG to 18FFES for each lesion was also calculated.
Data Analysis
All patients were divided into 3 groups. The first group was
high-risk endometrial carcinoma with FIGO stage higher than Ib

PET INDEX FOR ENDOMETRIAL DIAGNOSIS • Tsujikawa et al.

1599

or histologic grade higher than grade 1. The second group was
low-risk carcinoma with FIGO stage Ib or Ia and histologic grade
1. The third group was endometrial hyperplasia. SUVs for 18FFDG and 18F-FES and the 18F-FDG–to–18F-FES ratio werecompared among the 3 groups by 1-way ANOVA with a post
hoc Games–Howell test, which has robustness for analysis even in
unequal variance. Differences in tracer accumulation were also
compared between the 2 tracers using a paired t test. Statisticalanalysis was performed using a software package (SPSS for
Microsoft Windows, version 11.5.1 J; SPSS Inc.).
Receiver-operating-characteristic (ROC) analysis was performed to determine diagnostic accuracy and the optimal cutoff
value to differentiate high- versus low-risk groups and low-riskversus hyperplasia groups using MedCalc (version 7.6.0.0; MedCalc Software). The area under the ROC curve (AUC) provided ameasure for the accuracy of a diagnostic test by PET parameters.
The diagnostic accuracy of MRI, compared with postoperative
definitive diagnosis, was evaluated by an ability to distinguishcarcinoma in advanced stages (FIGO stage $ Ic) from early stages(FIGO stage # Ib) irrespective of histologic grade. The accuracyof MRI findings and PET parameters was also compared using the
McNemar test. A probability value of less than 0.05 was considered to indicate a significant difference.
RESULTS
SUVs and Ratio

Table 1 summarizes patient characteristics including
tumor stage and lesion size. Thirteen patients were premenopausal and 18 were postmenopausal. The mean SUVs
and 18F-FDG–to–18F-FES ratios for each group are given in
Table 2. Patients with high-risk endometrial carcinoma
showed a significantly higher accumulation of 18F-FDG
than 18F-FES (P , 0.0001, paired t test), whereas patientswith low-risk carcinoma did not show a significant difference between 18F-FDG and 18F-FES uptake. In contrast,
endometrial hyperplasia showed a significantly higher uptake for 18F-FES than 18F-FDG (P , 0.005) in the primarytumors. Figure 1 shows the tendencies toward an increasein 18F-FDG uptake and a decrease in 18F-FES as diseaseprogressed to a higher stage or histologic grade. 18F-FDG
accumulation was not significantly different between highrisk and low-risk endometrial carcinoma, although hyperplasia showed significantly lower 18F-FDG accumulation
than did high-risk (P , 0.0001) and low-risk (P , 0.005)
carcinoma. 18F-FES PET showed a significant difference
between these 2 groups of carcinoma (P , 0.05). In Figure

2, high-risk carcinoma showed a significantly greater 18FFDG–to–18F-FES ratio than did low-risk carcinoma (P ,0.01) and endometrial hyperplasia (P , 0.005). Low-risk
carcinoma also showed a significantly higher 18F-FDG–
to–18F-FES ratio than hyperplasia (P , 0.0001).
ROC Analysis and Comparison with MRI

AUCs obtained from ROC analysis for distinction ofhigh- and low-risk carcinoma were 0.90, 0.81, and 0.72 forthe 18F-FDG–to–18F-FES ratio, 18F-FES SUV, and 18F-FDG
SUV, respectively, indicating that the 18F-FDG–to–18F-FES
ratio is the most informative index for differentiating aggressiveness of carcinoma although no significant difference was observed in AUCs by the z test. Table 3 shows thediagnostic accuracy for the 3 PET parameters and MRI
findings for distinction of high-risk from low-risk carcinoma. ROC analysis determined the optimal cutoff value foreach PET parameter to distinguish high- and low-risk
carcinoma. The optimal 18F-FDG–to–18F-FES cutoff ratioof 2.0 provided 73% sensitivity and 100% specificity, whichyielded the greatest accuracy of 86% among all PET
parameters and MRI. Because all lesions of endometrial
hyperplasia showed a low 18F-FDG–to–18F-FES ratio ofless than 0.5, a cutoff ratio of 0.5 could distinguish all casesof low-risk carcinoma from hyperplasia correctly, yielding
no false-positive findings and 100% accuracy. A cutoff 18FFDG SUV of 2.0 also differentiated malignant tumors frombenign lesions (Fig. 1). The accuracies of PET parametersand MRI findings were statistically compared, and a significant difference was observed between the 18F-FDG–
to–18F-FES ratio and 18F-FDG SUV (P , 0.005, McNemartest).
Representative Cases

Representative images of each group are given in Figures
3–5. Figure 3 shows high-risk endometrial carcinoma(FIGO stage Ic, histologic grade 2). MRI findings suggested
no myometrial invasion (stage Ia), and PET images showed
high 18F-FDG and moderate 18F-FES accumulation in the
primary tumor, with an 18F-FDG–to–18F-FES ratio of 2.5,
indicating high-risk carcinoma. Figure 4 is a case of lowrisk endometrial carcinoma (FIGO stage Ib, histologic
grade 1) showing high 18F-FDG and 18F-FES uptake withan 18F-FDG–to–18F-FES ratio of 1.3. MRI also indicatedearly-stage endometrial carcinoma with superficial myo-

TABLE 2. Regional SUVs and 18F-FDG–to–18F-FES SUV Ratio
18F-FDG SUVClass
Patients
High-risk carcinoma (stage $ Ic or grade $ 2)
11
9.9 6 2.6* (5.4–14.8)
Low-risk carcinoma (stage # Ib and grade 1)
11
7.1 6 3.7 (2.4–12.5)
Endometrial hyperplasia
9
1.5 6 0.3 (1.1–1.9)

18F-FES SUV

3.4 6 1.6 (1.3–6.3)
5.3 6 1.8 (2.1–8.1)
5.6 6 2.4y (2.7–11.0)

18F-FDG–to–18F-FES ratio

3.6 6 2.1 (1.3–7.4)
1.3 6 0.5 (0.5–1.8)
0.3 6 0.1 (0.2–0.4)*P , 0.0001.
y
P , 0.005 significantly higher between the 2 PET tracers (paired t test).
Values are mean 6 SD. Statistical significance for group comparison is given in Figures 1 and 2. Data in parentheses are ranges.

1600

THE JOURNAL OF NUCLEAR MEDICINE • Vol. 50 • No. 10 • October 2009

FIGURE 1. Box-and-whisker plots of uptake of each tracer
among 3 groups. Horizontal bars inside boxes indicate
median values. Error bars indicate farthest points that are
not outliers. Significant differences in 18F-FDG accumulation
were observed between hyperplasia and high-risk (P ,0.0001) or low-risk (P , 0.005) endometrial carcinoma. 18FFDG accumulation was not significantly different between
high-risk and low-risk carcinoma, although 18F-FES PET
showed significant difference between these 2 groups (P ,0.05). High-R 5 high-risk carcinoma; low-R 5 low-risk
carcinoma; NS 5 not significant.

metrial invasion (Ib). Endometrial hyperplasia had a highlevel of 18F-FES accumulation corresponding to the thickening of endometrium on MRI (Fig. 5). The 18F-FDG–
to–18F-FES ratio of this patient was 0.2.
DISCUSSION

Our recent PET study using 18F-FES and 18F-FDG
revealed that uterine tumors had opposite tendencies interms of 18F-FES and 18F-FDG accumulation, which represents ER expression and glucose metabolism, between
benign and malignant lesions (11). Thus, PET studies withthe 2 tracers were useful to provide pathophysiologic
information for the differential diagnosis of uterine tumors.
In the present study with a larger sample size of endometrial tumors, 2 PET images could distinguish endometrial
carcinoma from benign lesions with PET parameters of 18FFDG SUV and 18F-FDG–to–18F-FES ratio. Furthermore,
the regional 18F-FDG–to–18F-FES ratio and the 18F-FES
SUV could distinguish high-risk carcinoma (FIGO stage $Ic or histologic grade $ 2) from low-risk carcinoma (FIGO
stage # Ib and histologic grade 1). This index provided theinformation that endometrial carcinoma with an advanced
stage or a higher grade reduces estrogen dependency withan increase in glucose metabolism. In contrast, endometrial
hyperplasia showed a significantly low 18F-FDG–to–18FFES ratio of less than 0.5, indicating its preserved ER
expression without an increase in glucose consumption.

FIGURE 2. Box-and-whisker plots of 18F-FDG–to–18F-FES
SUV ratio among 3 groups. Significant differences wereobserved between high-risk and low-risk carcinoma (P ,0.01), between high-risk carcinoma and hyperplasia (P ,0.005), and between low-risk carcinoma and hyperplasia(P , 0.0001). High-R 5 high-risk carcinoma; low-R 5 lowrisk carcinoma.

Low-risk carcinoma with moderate-to-intense 18F-FDG andaccumulation is considered between high-risk
carcinoma and hyperplasia in terms of aggressiveness.
Several reports indicated that 18F-FDG PET is useful for
managing pre- and postoperative patients with endometrial
carcinoma mainly by detecting lymph node metastasis(14–17). The classification of tumor characteristics determined by 18F-FDG uptake and the 18F-FDG–to–18F-FES
ratio could play an important role in the differential
diagnosis of endometrial lesions and in deciding the therapeutic strategy. The cutoff 18F-FDG–to–18F-FES ratio of
0.5 and the 18F-FDG SUV of 2.0 could differentiate lowrisk carcinoma from hyperplasia, and all malignancies werecorrectly distinguished from benign lesions, with no falsepositive findings and 100% accuracy. Some characteristic
MRI findings of benign endometrial lesions such as endometrial hyperplasia and polyps were reported previously(18,19). Those specific findings are occasionally detected in
the case of relatively large tumor volume, whereas it is difficult to differentiate small-sized endometrial hyperplasia
from stage Ia carcinoma. PET, which characterizes tumor
biofunction, would be more reliable than MRI findings forthe preoperative diagnosis. Uterine tumors with estrogendependent function such as endometrial carcinoma may lose
their estrogen-dependent function, reduce ER expression,and increase glucose metabolism because of aberrant glycolysis with dedifferentiation. This functional transformation could have shown opposite tendencies of high glucose
metabolism and low 18F-FES accumulation in malignant
18F-FESPET INDEX FOR ENDOMETRIAL DIAGNOSIS • Tsujikawa et al.

1601

55–92
45–86
55–92
44–97
47–10050–93
8/10 (80%)
4/4 (100%)
13/17 (76%)

17/22 (77%)
15/22 (68%z)
17/22 (77%)

95% CI (%)
65–97

Accuracyn
19/22 (86%z)
95% CI (%)
49–95
n
11/14 (79%)

NPV
PPVSpecificity
Sensitivity

Parametern
95% CI (%)
n
95% CI (%)
n
95% CI (%)
18F-FDG–to–18F-FES
8/11 (73%)
39–94
11/11 (100%)
76–1008/8 (100%)
69–100
ratio (2.0)*
18F-FES SUV (4.4)*
9/11 (82%)
48–97
8/11 (73%)
39–94
9/12 (75%)
43–95
18F-FDG SUV (4.0)*
11/11 (100%)
76–100
4/11 (36%)
11–69
11/18 (61%)
36–83
MRIy
4/8 (50%)
16–84
13/14 (93%)
66–1004/5 (80%)
28–99*Optimal cutoff value.
yDiscrimination of stage $ Ic from # Ib irrespective of histologic grade.
z
P , 0.005 in comparison between 18F-FDG–to–18F-FES ratio and 18F-FDG SUV using McNemar test.
PPV 5 positive predictive value; NPV 5 negative predictive value.

TABLE 3. Diagnostic Accuracy in Differentiating High- and Low-Risk Carcinoma

1602

FIGURE 3. T2-weighted (A), contrast-enhanced
T1-weighted MR (B), 18F-FDG (C), and 18F-FES PET (D)images of 60-y-old woman with endometrial carcinoma(arrows). PET images showed intense 18F-FDG uptake (SUV,11.6) and moderate 18F-FES uptake (SUV, 4.7) in tumor.
Preoperative staging by MRI suggested no myometrial
invasion, whereas PET findings with an 18F-FDG–to–18FFES ratio of 2.5 indicated high-risk carcinoma. Postoperative histopathologic result was high-risk carcinoma with
FIGO stage Ic and histologic grade 2.

tumors, especially in high-risk carcinoma. This noninvasive
method could avoid unnecessary operations or invasive
whole-endometrium curettage, which is important for preserving women’s reproductive potential.
Functional PET is considered a promising method for
deciding on personalized treatment. Although it would be
difficult to determine the histologic grade of endometrial
lesions by pelvic MRI, PET scans with 18F-FES and 18FFDG can reflect tumor aggressiveness (invasiveness andgrade) using the index of 18F-FDG–to–18F-FES ratio. As
shown in the present study, the diagnostic accuracy of the
18F-FDG–to–18F-FES ratio was better than that of MRI in
distinguishing high-risk from low-risk carcinoma. Surgicalpathologic staging is now the standard of care for endometrial carcinoma (3). However, the role of comprehensive
surgical staging, especially pelvic and paraaortic lymphadenectomy for all patients, remains controversial. Several
reports asserted that patients with low-risk endometrial
carcinoma can be treated with hysterectomy only (20,21).
Avoiding lymphadenectomy decreases complications after
surgery. Patients with low-risk endometrial carcinoma determined by an 18F-FDG–to–18F-FES ratio of less than 2.0
may be able to avoid pelvic or paraaortic lymphadenectomy, although the cutoff values for PET parameters should
be validated prospectively using an independent patientgroup in further study because the cutoffs were optimized
from this particular dataset. To decrease unnecessary lymphadenectomy and establish a noninvasive evaluation
method for risk management in patients with endometrial

THE JOURNAL OF NUCLEAR MEDICINE • Vol. 50 • No. 10 • October 2009

carcinoma in stage Ia or Ib from stage Ic (or higher),
18F-FDG PET is considered to show a higher detection rate

FIGURE 4. Sagittal T2-weighted (A), contrast-enhanced
T1-weighted MR (B), 18F-FDG (C), and 18F-FES PET (D)images of 50-y-old woman with low-risk endometrial carcinoma (FIGO stage Ib and histologic grade 1, arrows). PET
images showed intense accumulation for both tracers inendometrial lesion. Region of 18F-FES uptake (SUV, 8.1)
appeared larger than that of 18F-FDG (SUV, 10.2) because of
18F-FES avidity in myometrial inner layer. 18F-FDG–to–18FFES ratio was 1.3.

carcinoma, further PET studies with a larger patient sample
and a long-term follow-up would be needed.
The present study included 2 patients with paraaortic andpelvic lymph node metastases (stage IIIc) among 11
patients high-risk carcinomas. All metastatic lymph nodes
were detected correctly by 18F-FDG PET, whereas thelymph nodes could not be identified with MRI in one of thepatients. Although MRI findings are superior to 18F-FDG
PET parameters in terms of the regional discrimination ofthan MRI for distant metastasis. In addition, histopathologic results of the cases with lymph node metastases were
grades 2 and 3, in which the primary sites showed far
higher 18F-FDG–to–18F-FES ratios (4.3 and 7.1, respectively) than the cutoff value. These results indicate that PET
studies with 18F-FDG and 18F-FES will reflect tumor
aggressiveness, which is useful information for the treatment of patients with endometrial lesions.
Although simple stage differentiation with PET parameters was also evaluated by ROC analysis, this method
could not differentiate early stages from advanced stages
because stage Ia or Ib carcinoma with grades 2 or 3 showeda tracer uptake tendency similar to that of the high-risk
group. Thus, we did not use this simple classification in thepresent study. The differentiation of high- and low-risktumors as determined here would be more appropriate forthe evaluation of tumor aggressiveness.
CONCLUSION

Endometrial carcinoma reduces estrogen dependencywith increased glucose metabolism as it progresses to ahigher stage or grade. The 18F-FDG–to–18F-FES ratio
calculated from 18F-FES and 18F-FDG PET is the mostinformative index reflecting tumor aggressiveness. This
index will be useful for noninvasive diagnosis and for
deciding on the appropriate therapeutic strategy for patientswith endometrial carcinoma.
ACKNOWLEDGMENTS

We thank the doctors of the Departments of Radiology andGynecology, Faculty of Medical Sciences, and the staff of the
Biological Imaging Research Center, University of Fukui, forclinical and technical support. This study was partly funded by
the Research and Development Project Aimed at Economic
Revitalization (Leading Project) from MEXT Japan and a
Grant-in-Aid for Scientific Research (20790887) and the 21stCentury COE Program (Medical Science) from the Japan
Society for the Promotion of Science.
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uterus. 18F-FDG–to–18F-FES ratio was 0.2.

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THE JOURNAL OF NUCLEAR MEDICINE • Vol. 50 • No. 10 • October 2009