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                                                                                                                                                ORIGINAL RESEARCH
                                                             Uterine Tumors: Pathophysiologic
                                                             Imaging with 16 -[18F]fluoro-17 -
                                                             estradiol and 18F Fluorodeoxyglucose




                                                                                                                                               NUCLEAR MEDICINE
                                                             PET—Initial Experience1
Tetsuya Tsujikawa, MD
                                                                  Purpose:    To clarify prospectively the relationship between estrogen
Yoshio Yoshida, MD, PhD
                                                                              receptor (ER) expression and glucose metabolism by using
Tetsuya Mori, PhD
                                                                              16 -[18F]fluoro-17 -estradiol (FES) and fluorine 18 (18F)
Tetsuji Kurokawa, MD, PhD                                                     fluorodeoxyglucose (FDG) positron emission tomography
Yasuhisa Fujibayashi, PhD                                                     (PET) in patients with benign and malignant uterine tu-
Fumikazu Kotsuji, MD, PhD                                                     mors.
Hidehiko Okazawa, MD, PhD
                                                              Materials and   The institutional review board approved this study, and
                                                                  Methods:    informed consent was obtained from all subjects. FES and
                                                                              FDG PET studies were performed in 38 patients (mean
                                                                              age, 54.1 years    14.0 [standard deviation]) with benign
                                                                              and malignant uterine tumors to compare differences in
                                                                              tracer accumulation. Regional values of tracer uptake
                                                                              were evaluated by using standardized uptake value (SUV),
                                                                              a normalized value corrected by using injection dose and
                                                                              body weight.

                                                                   Results:   Patients with endometrial carcinoma showed significantly
                                                                              greater mean SUV for FDG (9.6 3.3) than for FES (3.8
                                                                              1.8) (P     .005). Patients with endometrial hyperplasia
                                                                              showed significantly higher mean SUV for FES (7.0 2.9)
                                                                              than for FDG (1.7 0.3) (P .05). Patients with leiomy-
                                                                              oma showed significantly higher mean SUV for FES (4.2
                                                                              2.4) than for FDG (2.2      1.1) (P   .005), and patients
                                                                              with sarcoma showed opposite tendencies for tracer accu-
                                                                              mulation. Tracer uptake in patients with endometrial car-
                                                                              cinoma was significantly higher for FDG (P      .001) and
                                                                              significantly lower for FES (P .05) when compared with
                                                                              values in patients with endometrial hyperplasia. On the
                                                                              other hand, patients with sarcoma showed a significantly
                                                                              higher uptake for FDG (P .005) and a significantly lower
                                                                              uptake for FES (P       .05) compared with patients with
                                                                              leiomyoma.

                                                                Conclusion:   ER expression and glucose metabolism of uterine tumors
                                                                              measured by using PET showed opposite tendencies. PET
1
  From the Biomedical Imaging Research Center (T.T.,                          studies with both FES and FDG could provide pathophysi-
T.M., Y.F., H.O.) and Department of Gynecology (Y.Y.,                         ologic information for the differential diagnosis of uterine
T.K., F.K.), Faculty of Medical Sciences, University of                       tumors.
Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji-cho, Fukui
910-1193, Japan. Received August 3, 2007; revision re-
                                                                               RSNA, 2008
quested September 28; revision received October 25;
accepted December 28; final version accepted February
6, 2008. Supported in part by Research and Development
Project Aimed at Economic Revitalization (Leading Project)
from MEXT Japan, and 21st Century COE Program (Medi-
cal Science) from Japan Society for the Promotion of
Science. Address correspondence to H.O. (e-mail:
okazawa@u-fukui.ac.jp).

    RSNA, 2008


Radiology: Volume 248: Number 2—August 2008                                                                                              599
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                              Tsujikawa et al




P
       ositron emission tomography (PET)         for primary tumors is inferior to that of    suspected of being malignant at cyto-
       with fluorine 18 (18F) fluorode-            magnetic resonance (MR) imaging (6–          logic analysis, ultrasonography, or MR
       oxyglucose (FDG) has been used            8). This is because the size of the tumor    imaging, participated in this study.
for diagnosis of gynecologic malignant           and inflammatory changes of the lesion        Nineteen women were premenopausal
tumors and is considered to be superior          may affect PET imaging and FDG accu-         and 19 women were postmenopausal.
to conventional imaging methods in di-           mulation. FDG uptake in the genital or-      None of them received any previous
agnostic accuracy for detection of meta-         gans is affected by the menstrual cycle,     treatment or therapy before this study.
static lesions and local recurrence (1–          as well (9,10). Additional physiologic in-   Definitive diagnosis was determined
5). However, the diagnostic accuracy             formation other than glucose metabo-         by using postoperative histopathologic
                                                 lism may improve the diagnostic accu-        analysis (n     30) or at least 6 months
                                                 racy of PET.                                 of follow-up by using cytologic analysis
 Advances in Knowledge                               16 -[18F]fluoro-17 -estradiol (FES)       (n     3) or clinical imaging (n     5, all
      Estrogen receptor expression and           is an 18F-labeled compound of estra-         with fibroids). Final diagnoses were
      glucose metabolism of uterine tu-          diol, the most bioactive type of estro-      endometrioid adenocarcinoma (n
      mors measured by using PET with            gen, and is used for the detection of        9), endometrial hyperplasia (n         4),
      16 -[18F]fluoro-17 -estradiol               estrogen receptor (ER)–positive or-          leiomyoma (n       21), and uterine sar-
      (FES) and 18F fluorodeoxyglucose            gans and diseases (11,12). FES PET           coma (leiomyosarcoma, n          1; carci-
      (FDG) showed opposite patterns             imaging is well established in patients      nosarcoma, n         3). In five patients
      between benign and malignant               with ER-positive breast cancer for di-       with leiomyoma who did not receive
      lesions, providing pathophysio-            agnosis, staging, and posttherapeutic        surgical treatment, a clinical decision
      logic information for differential         follow-up (13–18). Investigators in          was made by using results of follow-up
      diagnosis.                                 previous studies (13–15) reported            studies with MR imaging and FDG
      Patients with endometrial carci-           that FES accumulation was well asso-         PET. These results showed that there
      noma showed a significantly                 ciated with the concentration of ER in       was no change in size and intensity, as
      higher accumulation of FDG than            in vitro measurements, and it could          well as no increase in FDG accumula-
      of FES in the primary tumors               therefore enable in vivo noninvasive         tion, in the lesions. Four of 21 patients
      (mean standardized uptake value            measurement of ER density.                   with leiomyoma (including one woman
      [SUV], 9.6 3.3 vs 3.8 1.8;                     The purpose of our study was to          with four lesions, one woman with
      P .005), whereas those with                clarify prospectively the relationship be-   three lesions, and two women with
      endometrial hyperplasia showed a           tween ER expression and glucose me-          two lesions each) had multiple lesions
      significantly higher uptake for FES         tabolism by using FES and FDG PET            assessed with MR imaging. Our study
      than for FDG (mean SUV, 7.0                in patients with benign and malignant        received institutional review board ap-
      2.9 vs 1.7 0.3; P .05).                    uterine tumors.                              proval, and informed consent was ob-
      In patients with smooth-muscle                                                          tained from all subjects.
      tumors of the uterus, leiomyoma
      showed a significantly higher up-            Materials and Methods
      take for FES than for FDG (mean
      SUV, 4.2 2.4 vs 2.2 1.1; P                 Subjects
      .005), whereas leiomyosarcoma              Thirty-eight consecutive patients (mean      Published online before print
      showed higher accumulation of              age, 54.1 years 14.0 [standard devi-         10.1148/radiol.2482071379
      FDG and lower accumulation of              ation]), with uterine tumors that were       Radiology 2008; 248:599 – 605
      FES (mean SUV, 6.4 4.3 vs
      1.6 0.6; P .11).                                                                        Abbreviations:
      FDG uptake for endometrial car-             Implications for Patient Care               ER estrogen receptor
                                                                                              FDG 18F fluorodeoxyglucose
      cinoma was significantly higher                 PET studies with both FES and            FES 16 -[18F]fluoro-17 -estradiol
      than it was for endometrial hy-                FDG could provide information            SUV standardized uptake value
      perplasia (P .001), and FES                    for the differential diagnosis of
                                                                                              Author contributions:
      uptake was significantly lower                  uterine tumors, which could help
                                                                                              Guarantors of integrity of entire study, T.T., H.O.; study
      for endometrial carcinoma than                 clinicians avoid inappropriate sur-
                                                                                              concepts/study design or data acquisition or data analy-
      it was for endometrial hyperpla-               gical operations and invasive            sis/interpretation, all authors; manuscript drafting or
      sia (P .05).                                   whole endometrial curettage.             manuscript revision for important intellectual content, all
      FDG uptake was significantly                    FES PET could be used to evalu-          authors; manuscript final version approval, all authors;
      higher (P .005) and FES uptake                 ate the response of ER-positive          literature research, T.T., H.O.; clinical studies, T.T., Y.Y.,
      was significantly lower (P .05)                 endometrial carcinoma, as well as        T.M., T.K., F.K., H.O.; statistical analysis, T.T., Y.Y., H.O.;
                                                                                              and manuscript editing, T.T., Y.F., F.K., H.O.
      for leiomyosarcoma than it was                 that of large uterine leiomyoma,
      for leiomyoma.                                 to hormonal therapy.                     Authors stated no financial relationship to disclose.


600                                                                                                      Radiology: Volume 248: Number 2—August 2008
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                                    Tsujikawa et al




PET Procedures                                   tions. The reconstructed images were                         tively). SUVs of three patients with car-
All patients underwent whole-body PET            then converted to a semiquantitative                         cinosarcoma were obtained from the
with FES and FDG to compare differ-              image corrected by the injection dose                        sarcoma-rich region of each tumor,
ences in tracer accumulation. Two                and the subject’s body weight (stan-                         which was diagnosed as leiomyosar-
scans were obtained on two separate              dardized uptake value [SUV]) for data                        coma from MR imaging findings.
days within 1 week in random se-                 analysis.                                                        In patients with multiple lesions,
quence. In premenopausal patients, one                                                                        SUVs for each patient were averaged.
patient underwent FES PET at the men-            Data Analysis                                                The FDG/FES ratio of the mean SUV for
strual phase, eight patients underwent           All subjects underwent MR imaging                            each lesion was also calculated.
it at the proliferative phase, and five           during the time between the two PET
patients underwent it at the secretory           examinations, or within 1 week from                          Statistical Analysis
phase. Six patients underwent FDG PET            them, for diagnosis and to obtain ana-                       The mean SUVs of the lesions were
at the proliferative phase, and eight pa-        tomic information about the pelvic or-                       compared between diseases by using
tients underwent it at the secretory             gans. T1- and T2-weighted images in                          analysis of variance with a post hoc
phase. The other five patients had irreg-         the sagittal and coronal planes were                         Fisher protected least-significant dif-
ular menstruation, and, therefore, it            acquired with a 1.5-T superconducting                        ference test. Differences in tracer ac-
was unclear in what phase of the men-            MR imaging system (Signa; GE Medi-                           cumulation also were compared be-
strual cycle the studies were performed.         cal Systems). For T1-weighted MR im-                         tween the two tracers by using a
We used a whole-body tomographic                 ages, the repetition time msec/echo                          paired t test. The FDG/FES ratios of
scanner (Advance; GE Medical Sys-                time msec was 533/8, and that for T2-                        mean SUV were compared among the
tems, Milwaukee, Wis), which permits             weighted images was 4700/90.                                 four groups by using analysis of vari-
simultaneous acquisition of 35 image                 Circular regions of interest with a                      ance and the post hoc test. A probabil-
sections in a two-dimensional acquisi-           fixed size of 8 mm in diameter were                           ity value of less than .05 was consid-
tion mode with intersection spacing of           drawn on the lesions to obtain the lo-                       ered to indicate a significant difference.
4.25 mm. Performance tests showed                cal SUV. Individual MR images were                           Statistical analysis was performed by us-
the intrinsic resolution of the scanner to       referenced for placement of regions of                       ing a software package (StatView, ver-
be 4.0 –5.3 mm in the axial direction (z-        interest in the appropriate region                           sion 5.0 for Windows; SAS Institute,
axis) and 4.6 –5.7 mm in the transaxial          after PET and MR images were coreg-                          Cary, NC).
direction (xy plane).                            istered (Body Guide; Advance Bio-
     18
       F FES was synthesized by using the        logic, Toronto, Canada). Two or three
method reported elsewhere (11,19). The           sagittal or coronal planes with 6-mm                            Results
specific activity was 100 –200 GBq/               thickness were used to obtain SUV at                         The mean SUVs for each disease are
  mol, and radiochemical purity was              the center of the lesion. A single sec-                      given in the Table. Patients with endo-
greater than 99%. For each study with            tion at the center of the lesion was                         metrial carcinoma showed a signifi-
FES and FDG PET, approximately 185               used when the lesion was small and                           cantly higher accumulation of FDG than
MBq of tracer was administered into              substantial partial volume effects on                        of FES in the primary tumors (P
the antecubital vein. Before tracer ad-          the mean SUV value were expected.                            .005). In contrast, patients with endo-
ministration, patients fasted at least 4         The same numbers of regions of inter-                        metrial hyperplasia showed a signifi-
hours for each study. Fifty minutes after        est were drawn on the FES and FDG                            cantly higher uptake for FES than for
the tracer injection, the patient was po-        PET images in each patient by using                          FDG (P         .05). In patients with
sitioned supine in the PET scanner, and          similarly placed uterine sections. The                       smooth-muscle tumors of the uterus,
a 16-minute emission scan was ob-                regions of interest were placed by two                       those with leiomyomas showed a sig-
tained, with 3-minute scans obtained at          radiologists (T.T. and H.O., with 8                          nificantly higher uptake for FES than
the pelvic region (two bed positions)            and 19 years of experience, respec-                          for FDG (P      .005), whereas leiomyo-
and 2-minute scans obtained in each re-
maining region (five bed positions) to
completely cover the region from the
head to the inguinal areas. Postinjection           Mean SUV in Tumors of the Uterus
transmission scans of 2 minutes at the
pelvis and 1 minute in other areas were             Tumor                            No. of Patients          FES                        FDG
obtained after the emission scans by us-             Endometrial carcinoma            9                       3.8    1.8 (1.3–6.9)       9.6   3.3 (3.7–15.2)
ing a germanium 68/gallium 68 rod                    Endometrial hyperplasia          4                       7.0    2.9 (4.5–11.0)      1.7   0.3 (1.3–1.9)
source for attenuation correction. The               Leiomyosarcoma                   4                       1.6    0.6 (0.9–2.3)       6.4   4.3 (2.4–10.2)
PET data were reconstructed by the                   Leiomyoma                       21                       4.2    2.4 (1.6–10.5)      2.2   1.1 (1.3–5.6)
iterative reconstruction method, with
                                                    Note.—Values are the mean   standard deviation. Numbers in parentheses are ranges.
selection of 14 subsets and two itera-

Radiology: Volume 248: Number 2—August 2008                                                                                                                     601
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                                     Tsujikawa et al




sarcomas and carcinosarcomas showed a                    rizes the difference in tracer accumu-                 with endometrial hyperplasia (P
higher concentration for FDG and a                       lation of the two tracers for four dis-                .05). When sarcoma and leiomyoma
lower accumulation for FES. The tracer                   eases. In the comparison of uterine                    of the uterus were compared, FDG
accumulation pattern was different be-                   endometrial neoplasms, FDG uptake                      uptake was significantly greater (P
tween benign and malignant tumors for                    in patients with endometrial carci-                    .005), whereas FES uptake was signif-
both endometrial and myometrial dis-                     noma was significantly higher than it                   icantly lower (P       .05), in patients
eases.                                                   was in those with hyperplasia (P                       with sarcoma than it was in those with
    Group analysis by using analysis of                  .001), whereas FES uptake was signif-                  leiomyoma.
variance featured a pattern of each                      icantly lower in patients with endome-                     Representative images of each dis-
tracer accumulation. Figure 1 summa-                     trial carcinoma than it was in patients                ease are shown in Figures 2–5. Pa-
                                                                                                                tients with endometrial carcinoma of
                                                                                                                the uterus showed high FDG accumu-
 Figure 1
                                                                                                                lation and moderate FES accumulation
                                                                                                                (Fig 2). All patients with endometrial
                                                                                                                carcinoma had high FDG accumula-
                                                                                                                tion with SUV of 3 or higher, and each
                                                                                                                patient showed a lower uptake for FES
                                                                                                                than for FDG. Patients with endome-
                                                                                                                trial hyperplasia had a high level of
                                                                                                                FES accumulation; however, at FDG
                                                                                                                PET, patients did not show a higher
                                                                                                                uptake in endometrial tissue com-
                                                                                                                pared with the muscle layer of the
                                                                                                                uterus (Fig 3). Figure 4 shows images
                                                                                                                of multiple leiomyomas of the uterus.
                                                                                                                FDG PET showed a relatively diffuse
                                                                                                                uptake pattern in all of the leiomyo-
 Figure 1: Graphs show differences in tracer accumulation among four diseases. Significant differences in        mas with SUV of less than 2, whereas
 FDG and FES accumulation were observed between malignant and benign diseases in both endometrium and           FES accumulation was different for
 myometrium. For sarcoma, difference between FES and FDG accumulation was not significant (NS) because           each tumor. Although the histologic
 standard deviation of FDG uptake was large. Each point is an average of mean SUV over regions of interest in   findings in all these tumors revealed
 one patient, and line segments connect mean SUVs of FES and FDG in same patient. Box plots represent           benign leiomyoma, the ER density var-
 mean standard deviation in all patients.                                                                       ied among them. Four of 21 patients
                                                                                                                with leiomyoma, including the patient
                                                                                                                in Figure 4 who had four lesions, had
                                                                                                                multiple lesions. Another patient had
 Figure 2                                                                                                       three lesions and the remaining two
                                                                                                                patients had two lesions each with val-
                                                                                                                ues within the range of 3.5–7.6 for
                                                                                                                FES and 1.5–2.9 for FDG.
                                                                                                                    Most patients with leiomyoma had a
                                                                                                                higher uptake of FES than of FDG (Fig
                                                                                                                1). Leiomyosarcoma of the uterus also
                                                                                                                showed a different accumulation pat-
                                                                                                                tern between FDG and FES (Fig 1). Fig-
                                                                                                                ure 5 shows a case of carcinosarcoma
                                                                                                                with a sarcoma-rich area and carcinoma-
                                                                                                                rich area. The sarcoma-rich area dis-
                                                                                                                plays substantially lower FES accumula-
                                                                                                                tion compared with leiomyomas. The
                                                                                                                SUV ratios of FDG/FES for each lesion
                                                                                                                showed a significant difference among
                                                                                                                four diseases (P .001). The mean ra-
 Figure 2: Coronal (a) T2-weighted MR image, (b) FES PET scan, and (c) FDG PET scan in 40-year-old
                                                                                                                tios were 3.2 2.2 versus 0.26 0.08
 woman with uterine endometrial carcinoma (arrow). Endometrial carcinoma showed moderate FES accumula-
                                                                                                                for endometrial carcinoma and hyper-
 tion (SUV, 2.6) and high FDG accumulation (SUV, 10.6).
                                                                                                                plasia, respectively (P .01), and 4.7

602                                                                                                                    Radiology: Volume 248: Number 2—August 2008
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                                 Tsujikawa et al




                                                  Figure 3
4.4 versus 0.63      0.38 for leiomyosar-
coma and leiomyoma, respectively (P
.001). A cutoff value of 1.0 for this
ratio provided complete detection of
benign and malignant tumors among
the endometrial tumors (sensitivity,
100%; specificity, 100%), and only one
false-positive leiomyoma among the myo-
metrial tumors (sensitivity, 100%; speci-
ficity, 95.2%).


  Discussion
Our study aimed to clarify the relation-
ship between ER expression and glu-
cose metabolism by using FES and FDG
PET in patients with uterine tumors and
to evaluate whether the addition of ER
density information for various uterine
lesions could contribute to accurate di-
agnosis. The major finding of our study            Figure 3: (a) Sagittal T2-weighted MR image, (b) FES PET scan, and (c) FDG PET scan in 30-year-old
was that ER expression and glucose me-            woman with endometrial hyperplasia (arrow). MR image showed high accumulation in the endometrial lesion
tabolism of uterine tumors measured by            of hyperplasia (SUV, 5.6). FDG PET scan did not show a higher uptake compared with the muscle layer of the
using PET show opposite patterns be-              uterus (SUV, 1.9).
tween benign and malignant lesions.
18
   F-labeled FES is an analog of estra-
diol, and FES accumulation is well cor-
related with the concentration of ER
in in vitro measurements (13–15). Be-             Figure 4
cause FES PET is used for the detec-
tion of ER expression in estrogen-re-
lated diseases such as breast cancer
(13–18), it is possible to measure in
vivo ER density noninvasively. On the
other hand, FDG is a glucose analogue
that reflects the activity of glucose
transport proteins and the intracellu-
lar phosphorylation by hexokinase
(20). PET studies with both FES and
FDG can provide pathophysiologic in-
formation for the differential diagno-
sis of uterine endometrial neoplasias
(endometrial carcinoma and hyperpla-
sia) and myometrial tumors (sarcoma
and leiomyoma).
     The differential diagnosis between
endometrial cancer and endometrial hy-            Figure 4: (a) T2-weighted MR image, (b) FES PET scan, and (c) FDG PET scan in 39-year-old woman with
                                                  multiple uterine leiomyoma (arrowheads). FES accumulation varied among four leiomyomas (SUV, 4.7, 3.1,
perplasia is sometimes difficult even
                                                  2.6, 2.0), whereas FDG PET showed relatively diffuse uptake in all tumors (mean SUV, 1.7; range, 1.5–1.8).
when smear cytologic analysis, pelvic
MR imaging, and endometrial biopsy
are used. Whole endometrial curettage
may also be required. Noninvasive diag-          showed higher FDG and lower FES ac-                     of noninvasive differential diagnosis
nosis of endometrial hyperplasia is              cumulation, a finding that was in con-                   for endometrial lesions by using PET.
therefore valuable, especially for pre-          trast to that for benign lesions, which                     It remains controversial whether
serving women’s reproductivity. In our           showed high FES and low FDG uptake.                     leiomyosarcoma can be distinguished
study, malignant endometrial tumors              These results indicate the possibility                  from leiomyoma of the uterus by using

Radiology: Volume 248: Number 2—August 2008                                                                                                               603
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                             Tsujikawa et al




conventional imaging methods such as                  leiomyoma (26–29). Together, these re-            hormonal therapy, predominantly with
MR imaging (21,22). Combined PET ex-                  ports and our data suggest that FES PET           aromatase inhibitors. On the basis of
aminations with the use of FES and FDG                can be used to distinguish malignant              the findings in our study, a similar appli-
may solve this problem because the                    smooth-muscle tumors from benign                  cation of FES PET can be expected for
tracer accumulation pattern is different              leiomyomas.                                       evaluation of the responses of ER-posi-
between these tumor types (Fig 1). Pre-                   The FDG/FES SUV ratio showed                  tive endometrial carcinomas, as well as
vious investigations showed that estro-               significant differences between benign             large uterine leiomyomas, to hormonal
gens affect the genesis and development               and malignant tumors of the endome-               therapy.
of leiomyoma and that each tumor                      trium and the myometrium. This index                   Accumulation of FES in the endome-
grows monoclonally from a single cell                 enhances the tendency of FDG and                  trium may vary according to the men-
(23–25). Estrogens promote the pro-                   FES accumulation for each lesion                  strual cycle of the subject. However, a
gression of leiomyomas of the uterus.                 shown in Figure 1, and, thus, a high              previous study by our group (30)
These findings are consistent with the                 SUV ratio indicates a malignant lesion.           showed that the plasma level of endoge-
results of the present study, which                   Although a cutoff value of 1.0 for this           nous estrogen was not correlated with
showed variability in FES accumulation                ratio gave high diagnostic accuracy for           FES accumulation in the endometrium
for each tumor despite the diffuse mod-               benign and malignant tumors, further              of the uterus, and SUV in the myome-
erate FDG accumulation in cases of mul-               investigation is needed to evaluate the           trium of the uterus was relatively con-
tiple leiomyomas (Fig 4). It is difficult to           reliability of this new index because             stant in most healthy premenopausal
exclude malignancy in cases of degener-               only a small number of patients for               control subjects. Although most of our
ative uterine leiomyoma with strong                   two of the tumor groups (hyperplasia              patients with endometrial tumors were
FDG accumulation. However, intense                    and sarcoma) underwent scanning in                older women, and the influence of men-
FES uptake by the lesion at additional                our study.                                        strual cycle on the PET scans was as-
FES PET scanning would suggest that                       FES PET also is used for prediction           sumed to be small, further evaluation is
the lesion is a benign leiomyoma (Fig 1).             of the response of ER-positive advanced           still needed.
Although nearly 100% of uterine leiomyo-              breast cancers to hormonal therapies,                  Our study had some limitations. The
mas show expression of ER, ER expres-                 such as tamoxifen (16,17). Linden et al           direct comparison of SUVs for FDG and
sion in leiomyosarcoma is reported to                 (18) revealed that quantitative FES PET           FES may not be appropriate because
be significantly lower than it is in                   can be used to predict the response to            FES and FDG reflect quite different
                                                                                                        tracer kinetics and biodistribution. How-
                                                                                                        ever, the different tendencies of tracer
 Figure 5                                                                                               accumulation seen in the same window
                                                                                                        range for SUV indicated the possibility
                                                                                                        to use either SUV or a ratio of the two
                                                                                                        SUVs for distinction between benign
                                                                                                        and malignant lesions.
                                                                                                             Another limitation was the paramet-
                                                                                                        ric statistical analysis used to compare
                                                                                                        groups with relatively small sample sizes
                                                                                                        (n     4) for two groups. We applied the
                                                                                                        parametric statistical procedures because
                                                                                                        a normal distribution of SUVs in the
                                                                                                        uterus was observed in our previous
                                                                                                        study with FES PET in 16 healthy volun-
                                                                                                        teers (30). Although the statistical analy-
                                                                                                        sis used in the present study may not be
                                                                                                        robust because of the small sample sizes,
                                                                                                        our findings warrant further study with a
                                                                                                        larger sample size of patients.
                                                                                                             In conclusion, ER expression and
                                                                                                        glucose metabolism of uterine tumors
                                                                                                        measured by PET showed opposite pat-
                                                                                                        terns between benign and malignant le-
 Figure 5: (a) Sagittal T1-weighted MR image with contrast enhancement, (b) FES PET scan, and (c) FDG   sions. PET studies with both FES and
 PET scan in 75-year-old woman with uterine carcinosarcoma. Sarcoma-rich region of carcinosarcoma
                                                                                                        FDG could provide considerable nonin-
 showed low FES uptake (SUV, 0.9) and high FDG uptake (SUV, 9.9) (arrow). Arrowhead shows carcinoma-
                                                                                                        vasive information for the differential
 rich region detected by using postoperative microscopic pathologic analysis.
                                                                                                        diagnosis of uterine tumors.

604                                                                                                            Radiology: Volume 248: Number 2—August 2008
NUCLEAR MEDICINE: Estrogen, Glucose, and Uterine Tumors at PET                                                                             Tsujikawa et al




Acknowledgments: The authors thank Yuki-                ovarian uptake in pre- and postmenopausal       20. Chung JK, Lee YJ, Kim C, et al. Mechanisms
nori Kusaka, MD, and Takayoshi Hirai, MD, De-           patients: assessment by PET/CT. J Nucl Med          related to [18F]fluorodeoxyglucose uptake of
partment of Environmental Health, Faculty of            2004;45:266 –271.                                   human colon cancers transplanted in nude
Medical Sciences, and staff of the Department of                                                            mice. J Nucl Med 1999;40:339 –346.
                                                    10. Nishizawa S, Inubushi M, Okada H. Physio-
Gynecology, Biological Imaging Research Center,
                                                        logical 18F-FDG uptake in the ovaries and       21. Sahdev A, Sohaib SA, Jacobs I, et al. MR
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