Tatsuro Tsuchida

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.

Evaluation of62Cu labeled diacetyl-bis(N 4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer

Abstract62Cu labeled diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator-produced, positron-emitting tracer for hypoxic tissue imaging. From basic studies, the retention mechanism of62Cu-ATSM is considered to be closely related to cytosolic/microsomal bioreduction, a possible system for hypoxic bioreductive drug activation. In order to evaluate the characteristics of62Cu-ATSM, PET studies were performed in 4 normal subjects and 6 patients with lung cancer.62Cu-ATSM cleared rapidly from the blood with little lung uptake (0.43±0.09, uptake ratio; divided by the arterial input function) in normal subjects. Intense tumor uptake of62Cu-ATSM was observed in all patients with lung cancer (3.00±1.50). A negative correlation was observed between blood flow and flow-normalized62Cu-ATSM uptake in three of four patients. In contrast,62Cu-ATSM uptake was not related to that of18F-fluorodeoxyglucose. The negative correlation between blood flow and flow normalized62Cu-ATSM uptake suggests an enhancement of retention of62Cu-ATSM by low flow.62Cu-ATSM is a promising PET tracer for tumor imaging, which might bring new information for chemotherapeutic treatment as well as radiotherapy of hypoxic tumors.

18F-FDG PET of Common Enhancing Malignant Brain Tumors

OBJECTIVE The purpose of our study was to determine whether (18)F-FDG PET can be used to differentiate among common enhancing brain tumors such as lymphoma, high-grade glioma, and metastatic brain tumor. MATERIALS AND METHODS We evaluated 34 patients with an enhancing brain tumor on MRI, including seven lymphomas, nine high-grade gliomas, and 18 metastatic tumors. All patients also underwent FDG PET. For PET image analysis, regions of interest were placed over the tumor (T), contralateral cortex (C), and white matter (WM). Average and maximum pixel values were determined at each site. On the basis of these measurements, average and maximum standard uptake values (SUV(avg) and SUV(max)) were calculated, along with activity ratios (T/C(avg), T/WM(avg), T/WM(max), and T/C(max)), and comparisons among lesions were then made. RESULTS All parameters were significantly higher for lymphoma than for other tumors (p < 0.01). High-grade gliomas showed significantly higher SUV(avg) and SUV(max) than metastatic tumors (p < 0.05). Other parameters did not differ between lesion types. SUV(max) was the most accurate parameter for distinguishing lymphomas. Using an SUV(max) of 15.0 as a cutoff for diagnosing CNS lymphoma, only one high-grade glioma was found as a false-positive (SUV(max), 18.8). CONCLUSION FDG PET may be useful for differentiating common enhancing malignant brain tumors, particularly lymphoma versus high-grade glioma and metastatic tumor. FDG PET can provide useful information for distinguishing between lymphoma and other malignant enhancing brain tumors and is recommended when differential diagnoses are difficult to narrow using MRI alone.

Effects of Alendronate on Bone Metabolism in Glucocorticoid-Induced Osteoporosis Measured by 18F-Fluoride PET: A Prospective Study

Osteoporosis represents a significant side effect of glucocorticoid therapy, and alendronate has been reported to prevent this glucocorticoid-induced osteoporosis. Functional imaging with 18F-fluoride PET allows quantitative analysis of bone metabolism in specific skeletal regions. However, only a few studies have quantitatively determined bone turnover and metabolism in glucocorticoid-induced osteoporosis by radiologic imaging techniques including PET. The aim of this study was to examine changes in regional bone remodeling and turnover as measured by 18F-fluoride PET, the relationship between these measured changes and conventional bone metabolism parameters, and the effect of alendronate treatment. Methods: The study group consisted of 24 postmenopausal women (mean age, 59.7 y) who had various diseases, excluding rheumatoid arthritis, and had been treated with 10 mg or more of oral glucocorticoids (prednisolone equivalent) per day for more than 6 mo. Treatment with 5 mg of alendronate per day began at the time of study entry and continued for 12 mo. 18F-fluoride PET was performed at baseline, 3 mo, and 12 mo to determine localized bone turnover, and the results were compared with other bone metabolism parameters. Results: Lumbar spine standardized uptake values (SUVs) were significantly lower (P < 0.05) in the osteoporotic group (T-score ≤ −2.5) than in the group that was healthy or osteopenic (T-score > −2.5). Patients treated with alendronate for 12 mo exhibited significant decreases in serum bone-specific alkaline phosphate (P < 0.05), urinary N-telopeptide for type I collagen (P < 0.01), lumbar spine SUV (P < 0.01), and femoral neck SUV (P < 0.01) in association with a gradual increase in bone mineral density (BMD) of the lumbar spine relative to the baseline value (P < 0.05). Although there was a significant correlation between BMD and SUV in the lumbar spine at baseline (P < 0.05), there was no correlation between the 2 variables at 12 mo of treatment with alendronate. Conclusion: Alendronate treatment resulted in significant decreases in bone metabolism and turnover in the lumbar spine. It also led to an increase in BMD of the lumbar spine in patients with glucocorticoid-induced osteoporosis. Our findings suggest that antiresorptive therapy has a direct bone-metabolism effect on skeletal kinetics in glucocorticoid-induced osteoporosis at the clinically important site of the lumbar spine.

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.

Grading of brain glioma with 1-11C-acetate PET: comparison with 18F-FDG PET

UNLABELLED The objective of this study is to reevaluate the clinical significance of 1-11C-acetate (ACE) positron emission tomography (PET) in patients with brain glioma, in comparison with 18F-fluorodeoxyglucose (FDG) PET. METHODS Ten patients with histologically proven glioma were included in this study. They underwent PET examination with both FDG and ACE on separate days. For ACE PET, 20-min data acquisition was performed just after the administration of 740 MBq of ACE; 10-20-min data were used for the analysis. FDG PET data acquisition for 10 min started 60 min postinjection of 370 MBq of FDG, approximately. Both reconstructed images were converted to standardized uptake value (SUV) images for patient body weight and injected dose. Regions of interest were placed on the tumor and the contralateral cerebral cortex, and SUV and tumor-to-cortex ratio (T/C) were calculated; these values were compared between high- and low-grade gliomas. RESULTS SUV and T/C of ACE PET showed significant difference (SUV: 2.63+/-0.46 vs. 1.85+/-0.56, P=.03; T/C: 2.36+/-0.63 vs. 1.14+/-0.36, P=.02). In contrast, FDG PET revealed no significant difference in SUV or T/C between high- and low-grade gliomas (SUV: 7.13+/-4.31 vs. 4.71+/-1.27, P=.31; T/C: 0.98+/-0.55 vs. 0.62+/-0.09, P=.22). CONCLUSION This preliminary study revealed that ACE PET is a promising tracer for the grading of brain glioma.

Copper-62 ATSM as a hypoxic tissue tracer in myocardial ischemia

Copper-62 labeled diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator produced positron-emitting tracer for hypoxic tissue imaging. To clarify the usefulness of62Cu-ATSM for myocardial ischemia,62Cu-ATSM PET was performed in 7 patients with coronary artery disease. Increased myocardial uptake of62Cu-ATSM was observed (myocardium/blood ratio: 3.09) in one patient with unstable angina, who had increased18F-fluorodeoxyglucose (18F-FDG) uptake under the fasting condition. The other 6 patients, who were clinically stable, did not have increased62Cu-ATSM uptake, although abnormal18F-FDG uptake was seen in 4 patients. This preliminary study suggests that62Cu-ATSM is a promising PET tracer for hypoxic imaging in acute ischemia.

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.

The Effectiveness of 18F-FDG PET/CT Combined with STIR MRI for Diagnosing Nodal Involvement in the Thorax

The purpose of this study was to compare the efficacy of short-τ inversion-recovery (STIR) MRI and 18F-FDG PET/CT for the detection of metastasis in mediastinal and hilar lymph nodes in patients with lung cancer. Methods: Ninety-three patients with known or suspected lung cancer with mediastinal and hilar lymph node swelling underwent STIR MRI and 18F-FDG PET/CT examinations. STIR MRI scans were obtained with a 2% copper sulfate phantom placed along the back of each patient, with the lymph node–to–phantom ratio calculated for quantitative analysis. For qualitative analysis, the results of all STIR MRI scans were evaluated using a 5-point visual scoring system. To evaluate the diagnostic capabilities of STIR MRI and 18F-FDG PET/CT, we used receiver-operating-characteristic curve analysis to determine the optimal thresholds for the lymph node–to–phantom ratio, visual score, and maximal standardized uptake value. Further, the capability of each to determine N-stage was compared in each patient using the McNemar test. Results: A total of 137 lymph nodes (82 malignant lesions, 55 benign lesions) were analyzed. When optimal threshold values were adopted, the quantitative and qualitative sensitivity, specificity, and accuracy of STIR MRI were not significantly different from those of 18F-FDG PET/CT. However, 18F-FDG PET/CT in combination with qualitative STIR MRI analysis had a significantly higher capability to detect nodal involvement on an individual-patient basis (96.9% specificity, 90.3% accuracy) than did 18F-FDG PET/CT alone (65.6% specificity, 81.7% accuracy). Conclusion: We found that the diagnostic capability of STIR MRI was not significantly different from that of 18F-FDG PET/CT. However, when those methods were combined, the diagnostic capability for N-staging was significantly improved.

Visualization of the cervical spinal cord with FDG and high-resolution PET.

PURPOSE Our aim was to evaluate the visibility of the cervical spinal cord with [18F]2-fluoro-2-deoxyglucose (FDG) and a high-resolution PET scanner and to quantify the glucose utilization by the cervical cord. METHOD Twenty-one normal subjects and three cervical myelopathy patients were studied. The visibility of the cervical spinal cord in sagittal and coronal sections was evaluated. The metabolic rate of glucose (MRGlu) and standardized uptake value (SUV) of FDG in the cord were calculated. RESULTS The entire cervical spinal cord was clearly visualized in 57% of the subjects: the upper cord in 81%, the middle cord in 73%, and the lower cord in 57%. The MRGlu of the normal cord was 1.93 +/- 0.37 mg/100 g/min. SUV was constant across all the vertebral levels and negatively correlated with subject age. In the myelopathy patients, the SUV of the entire cervical cord was lower than in the age-matched normal subjects. CONCLUSION These preliminary results indicate that the cervical spinal cord can be visualized as a normal structure in routine head and neck PET imaging and that FDG-PET may provide quantitative information about spinal cord disorders.