Tetsuji Kurokawa

Expression of GLUT-1 glucose transfer, cellular proliferation activity and grade of tumor correlate with [F-18]-fluorodeoxyglucose uptake by positron emission tomography in epithelial tumors of the ovary

We evaluated whether tracer FDG uptake, quantified as an SUV by PET in ovarian epithelial tumors, correlates with clinical stage, tumor grade, cell proliferation and glucose metabolism, all of which are biomarkers for response to chemotherapy, prognosis and overall survival in ovarian cancer patients. Seventeen patients suspected of having ovarian cancer by physical examination, tumor marker analysis and anatomic imaging (such as sonography, CT and/or MRI) underwent whole‐body FDG‐PET within the 2 weeks prior to surgery. Seventeen epithelial ovarian tumor specimens (13 malignant tumors, 5 at stage I, 2 at stage II, 6 at stage III; 2 borderline tumors; and 2 benign lesions) were available for pathologic evaluation. They were graded histopathologically, and immunohistochemistry for MIB‐1 (proliferation index marker) and GLUT‐1 was performed. Correlation between FDG uptake and clinical stage, GLUT‐1 expression, MIB‐1 LI and histologic grading score was determined. No positive correlation was observed between FDG uptake and clinical stage (p = 0.14). Intensity of GLUT‐1 expression (r = 0.76, p = 0.001), MIB‐1 LI (r = 0.457, p = 0.014) and histologic grading score (r = 0.692, p = 0.005) showed statistically significant positive correlations with FDG uptake. Stepwise logistic regression analysis revealed that expression of GLUT‐1 transporters was the strongest parameter (r = 0.760, p = 0.0004) by which to predict positive FDG uptake. Therefore, glucose consumption, as determined by analysis of SUVs in FDG‐PET, may be a noninvasive biomarker for ovarian epithelial tumors.

Uterine Tumors: Pathophysiologic Imaging with 16α-[18F]fluoro-17β-estradiol and 18F Fluorodeoxyglucose PET—Initial Experience

PURPOSE To clarify prospectively the relationship between estrogen receptor (ER) expression and glucose metabolism by using 16alpha-[(18)F]fluoro-17beta-estradiol (FES) and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with benign and malignant uterine tumors. MATERIALS AND METHODS The institutional review board approved this study, and 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 leiomyoma 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 accumulation. Tracer uptake in patients with endometrial carcinoma 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 studies with both FES and FDG could provide pathophysiologic information for the differential diagnosis of uterine tumors.

Functional Images Reflect Aggressiveness of Endometrial Carcinoma: Estrogen Receptor Expression Combined with 18F-FDG PET

The 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 16α-18F-fluoro-17β-estradiol (18F-FES) and 18F-FDG PET reflect clinicopathologic features in patients with endometrial tumors. Methods: A total of 22 patients with endometrial adenocarcinoma and 9 with endometrial hyperplasia (mean age, 56.0 ± 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) and the 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 ± 2.1) than did low-risk carcinoma (1.3 ± 0.5, P < 0.01) and hyperplasia (0.3 ± 0.1, P < 0.005). Low-risk carcinoma showed a significantly 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/18F-FES 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 be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial carcinoma.

Evaluation of positron emission tomography with tracer 18-fluorodeoxyglucose in addition to magnetic resonance imaging in the diagnosis of ovarian cancer in selected women after ultrasonography.

Objective: To determine whether positron emission tomography (PET) with tracer 18-fluorodeoxyglucose (FDG-PET) yields additional information in the diagnosis of malignancy compared with magnetic resonance imaging (MRI) findings in selected women after screening for ovarian masses by ultrasonography (US). Methods: After 49 patients were screened by US and physical examination (including a pelvic examination) by 2 experienced gynecologic oncologists, 38 patients suspected of having ovarian cancer were enrolled in the study. All 38 underwent MRI and FDG-PET. The results of the histologic findings were used to assess the accuracy of the imaging findings. Results: Of the 38 women, 23 had malignant lesions and 15 had benign lesions. Magnetic resonance imaging, PET, and MRI with FDG-PET diagnoses had sensitivities of 91%, 78%, and 91%, respectively; specificities of 87%, 87%, and 87%, respectively; and diagnostic accuracy of 92%, 82%, and 92%, respectively. Conclusion: The addition of FDG-PET to MRI does not yield significant additional information for differentiation of benign from malignant ovarian masses in selected women after US.

18F-FES and 18F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

The aim of this study was to investigate the relationship between the tumor uptake of 16α-18F-fluoro-17β-estradiol (18F-FES) and 18F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors. Methods: Forty-seven patients with mesenchymal uterine tumors were studied with 18F-FES and 18F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERα, ERβ, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for 18F-FES and 18F-FDG were compared with the semiquantitative immunoreactive score (0–12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry. Results: 18F-FES uptake was significantly lower (P < 0.001) and the 18F-FDG uptake and SUV ratio of 18F-FDG to 18F-FES (18F-FDG/18F-FES ratio) (P < 0.005 and P < 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERα, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between 18F-FES SUV and immunohistochemistry scores of ERα, PR (P < 0.001), and PR-B (P < 0.005) as well as between 18F-FDG SUV and GLUT-1 and Ki-67 (P < 0.001). However, the 18F-FDG/18F-FES ratio showed significantly negative correlations with ERα, PR (P < 0.001), and PR-B (P < 0.005) and a positive correlation with Ki-67 LI (P < 0.001). In uterine sarcomas, ERα and 18F-FES SUV showed a positive correlation (P < 0.001) in a low SUV range, and the 18F-FDG/18F-FES ratio showed positive correlations with ERβ and GLUT-1 expression (P < 0.005). Conclusion: 18F-FES and 18F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The 18F-FDG/18F-FES ratio was correlated with Ki-67, GLUT-1, and ERβ in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.

Transverse uterine fundal incision for placenta praevia with accreta, involving the entire anterior uterine wall: a case series

To determine the feasibility and safety of transverse fundal incision with manual placental removal in women with placenta praevia and possible placenta accreta.

Additional value of 16α-[18F]fluoro-17β-oestradiol PET for differential diagnosis between uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [18F]fluorodeoxyglucose PET.

PurposePathological data suggest that the rate of oestrogen receptor (ER) expression in uterine sarcoma is significantly lower than in leiomyoma. The present study aimed to investigate whether ER expression using ER imaging agents for positron emission tomography (PET), of which the most successful has been 16α-[18F]-fluoro-17β-oestradiol (FES), is able to add useful information to the differential diagnosis of uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [18F]fluorodeoxyglucose (FDG) PET.MethodsA total of 76 patients with suspected uterine sarcoma based on ultrasound and magnetic resonance imaging findings from 2007 to 2010 were enrolled. Twenty-four of the present patients were referred for FES PET because of FDG PET findings that showed equivocal or positive FDG uptake. PET images were quantitatively evaluated with reference to histopathological findings. Receiver-operating characteristic analysis was performed to determine the optimal cutoff value to differentiate uterine sarcoma and leiomyoma.ResultsOf the 24 patients, 11 had a final diagnosis of uterine sarcoma, while 13 had leiomyoma. The sensitivity, specificity and accuracy of an FDG to FES standardized uptake value (SUV) ratio greater than 2.0 were significantly higher using Cochran’s Q test (p = 0.024) when compared with FDG PET greater than 3.0 alone (90.9 vs 81.8%, 92.3 vs 84.6% and 91.3 vs 83.3%, respectively).ConclusionAdditional FES PET findings confirmed uterine sarcoma in 91.3% of a selected group of patients with equivocal or positive FDG uptake.

Positron emission tomography in ovarian cancer: 18F-deoxy-glucose and 16α-18F-fluoro-17β-estradiol PET

The most frequently used molecular imaging technique is currently 18F-deoxy-glucose (FDG) positron emission tomography (PET). FDG-PET holds promise in the evaluation of recurrent or residual ovarian cancer when CA125 levels are rising and conventional imaging, such as ultrasound, CT, or MRI, is inconclusive or negative. Recently, integrated PET/CT, in which a full-ring-detector clinical PET scanner and a multidetector helical CT scanner are combined, has enabled the acquisition of both metabolic and anatomic imaging data using one device in a single diagnostic session. This can also provide precise anatomic localization of suspicious areas of increased FDG uptake and rule out false-positive PET findings. FDG-PET/CT is an accurate modality for assessing primary and recurrent ovarian cancer and may affect management. FDG-PET/CT may provide benefits for detection of recurrent of ovarian cancer and improve surgical planning. And FDG-PET has been shown to predict response to neoadjuvant chemotherapy and survival in advanced ovarian cancer. This review focuses on the role of FDG-PET and FDG-PET/CT in the management of patients with ovarian cancer. Recently, we have evaluated 16α-18F-fluoro-17β-estradiol (FES)-PET, which detects estrogen receptors. In a preliminary study we reported that FES-PET provides information useful for assessing ER status in advanced ovarian cancer. This new information may expand treatment choice for such patients.

Functional oestrogen receptor α imaging in endometrial carcinoma using 16α-[18F]fluoro-17β-oestradiol PET

PurposeTo investigate the correlation between uptake of 16α-[18F]fluoro-17β-oestradiol (FES) and expression of oestrogen receptors as well as other related immunohistochemistry markers, positron emission tomography (PET) was performed in patients with endometrial carcinoma before surgery.MethodsNineteen patients with endometrioid adenocarcinoma underwent preoperative PET studies with FES and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Standardized uptake values (SUVs) for each tracer and the regional FDG to FES SUV ratio were calculated using images after coregistration. PET values were compared with postoperative stage, differentiation grade and immunohistochemical scores including oestrogen receptor subtypes (ERα, ERβ), progesterone receptor B (PR-B), Ki-67 and glucose transporter 1 (GLUT1).ResultsFES uptake showed a significantly positive correlation with expression of ERα. The FDG to FES ratio showed a significantly negative correlation with expression of ERα and PR-B. The FES uptake and FDG to FES ratio did not correlate with expression of ERβ, Ki-67 or GLUT1. FDG uptake was not correlated with any of the immunohistochemical scores. The PR-B score was strongly correlated with the ERα score. Well-differentiated carcinoma (grade 1) showed a significantly higher FES uptake and significantly lower FDG to FES ratio than moderately or poorly differentiated carcinoma (grade 2–3). None of the PET parameters were significantly different between advanced-stage carcinoma (≥ stage IB) and early-stage carcinoma (IA) based on the Féderation International de Gynécologie et d’Obstétrique (FIGO) staging classification. Differentiation grade was the most closely correlated parameter to FES uptake and FDG to FES ratio by multivariate analyses.ConclusionFES PET combined with FDG would be useful for non-invasive evaluation of ERα distribution, as well as ERα function, which reflects differentiation grade in endometrial carcinoma.

Comparison of 18F-FDG PET and MRI in Assessment of Uterine Smooth Muscle Tumors

The purpose of this study was to prospectively determine whether combined MRI and 18F-FDG PET is more accurate than MRI in assessing nonbenign uterine smooth muscle tumors (USMTs). Methods: Seventy patients (mean age, 49 ± 10 y; range, 28–77 y) suspected of having nonbenign USMTs underwent both MRI and 18F-FDG PET before surgery. Results were evaluated using receiver-operating-characteristic (ROC) analyses and the Cochran Q test. Results: The area under the ROC curve for MRI with 18F-FDG PET was significantly higher than that for MRI (0.97 vs. 0.89, P < 0.05). Although multiple comparisons using the Cochran Q test were not significant, the sensitivity, specificity, and accuracy for MRI with 18F-FDG PET with probable nonbenign USMT cases considered to be positive were higher than those for MRI (93.3% vs. 73.3%; 92.7% vs. 85.5%; and 92.9% vs. 82.9%, respectively). Conclusion: MRI with 18F-FDG PET is useful in assessing nonbenign USMTs, as compared with MRI.