Seiji Kurata

Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

BACKGROUND [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. METHODS We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. RESULTS This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio=2.34; 95% confidence interval, 1.18-4.64; P=0.015] and OS (hazard ratio=2.80; 95% confidence interval, 1.12-6.96; P=0.003), whereas SUVmean and SUVmax had no significant association with PFS (P=0.693 and P=0.322, respectively) or OS (P=0.587 and P=0.214, respectively). CONCLUSIONS Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

The relationship between GLUT-1 and vascular endothelial growth factor expression and 18F-FDG uptake in esophageal squamous cell cancer patients.

Purpose: To examine the relationship between glucose transporter-1 (GLUT-1) and vascular endothelial growth factor (VEGF) expression and 18F-FDG uptake in esophageal squamous cell cancer patients. Materials and Methods: Fifty-seven patients (52 male and 5 female) were included in this study. 18F-FDG PET/CT was performed prior to the surgery. Immunohistochemistry was performed using postoperative histopathological specimens. The estimation of immunohistochemistry was conducted using scoring analysis. We investigated the correlations between maximum standardized uptake value (SUVmax) and GLUT-1/VEGF expressions/pathologic tumor length (p-tumor length), and the relationships between pathologic T (p-T) stage and GLUT-1/VEGF expressions/SUVmax and between lymph node metastasis (p-N) stage and GLUT-1/VEGF expressions/SUVmax. Results: SUVmax significantly correlated with GLUT-1 expressions and p-tumor length (GLUT-1: r = 0.475, P < 0.001; p-tumor length: r = 0.475, P < 0.001). SUVmax of the primary tumor had a significant relationship with p-T stage, p-N stage, and VEGF expression (p-T stage: P < 0.001; p-N stage: P = 0.037; VEGF expression: P = 0.009). There was a statistically significant difference between GLUT-1 expression and p-T stage/VEGF expression, but not p-N stage (p-T stage: P = 0.012; VEGF expression: P = 0.01; p-N stage: P = 0.572). VEGF expression had a significant relationship with p-T stage, but not with p-N stage (p-T stage: P = 0.032; p-N stage: P = 0.763). Conclusion: 18F-FDG uptake can be determined by GLUT-1 and VEGF. SUVmax would have a connection with the tumor progression and lymph node metastasis.

Prognostic value of SUVmax measurements obtained by FDG-PET in patients with non-small cell lung cancer receiving chemotherapy.

[(18)F]Fluorodeoxyglucose (FDG) uptake has been shown to correlate well with tumor proliferation rates. In patients with non-small cell lung cancer (NSCLC) receiving chemotherapy, we analyzed the relationships between the maximum standardized uptake value (SUVmax) obtained by FDG positron emission tomography (FDG-PET) and other clinical factors, and examined whether or not SUVmax could predict progression-free survival (PFS) and/or overall survival (OS). This retrospective study involved 62 consecutive NSCLC patients (35 male and 27 female: median age, 65 years). All patients underwent FDG-PET examination before treatment. As the first-line treatment, the patients received chemotherapy with (n=15) or without (n=47) radiotherapy. Survival curves were obtained by the Kaplan-Meier method, and differences in survival between subgroups were analyzed by the log-rank test and the Cox proportional hazards model. Significant correlations were observed between SUVmax and gender (P=0.006), histology (P<0.001), smoking status (P=0.049), stage (P=0.015), and treatment modality (P=0.008), but not other factors, including age (P=0.402) and performance status (P=0.421). The median SUVmax was 5.1 (25-75th percentile: 3.45-7.0) in patients with adenocarcinoma and 8.3 (25-75th percentile: 6.9-9.9) in those with other types of NSCLC. Adenocarcinomas showed significantly lower SUVmax than the other tumor types (P<0.001). Cox analysis adjusting for possible confounding factors, including gender, smoking status, histology and stage, demonstrated that the hazard ratios increased as the SUVmax increased in terms of both PFS (P=0.008) and OS (P=0.045), indicating that SUVmax predicts outcome independently of other clinical factors, such as histology and stage. Our findings indicate that FDG-PET examination can provide information useful for prognostication in NSCLC.

Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

ObjectiveThe aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device.MethodsBetween January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal 18F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital.ResultsOf the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device.ConclusionsIn cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future.

Improved breast cancer detection of prone breast fluorodeoxyglucose-PET in 118 patients.

ObjectiveTo prospectively evaluate the breast cancer detection of prone breast positron emission tomography (PET) images in comparison with supine whole-body PET images. Material and methodsOne hundred and eighteen female patients (age range 28–91 years) with 122 lesions suspected of having breast cancer underwent fluorine-18 fluorodeoxyglucose PET for preoperative staging. After the whole-body image was acquired, prone breast PET imaging was performed. The findings from both images were compared with the histopathologic results. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy were used to compare the diagnostic accuracy of prone breast PET images with that of whole-body PET images. ResultsSensitivity, specificity, positive predictive value, NPV, and accuracy of whole-body PET images were 83, 50, 97, 17, and 80%, and of prone breast PET images they were 95, 50, 96, 43, and 93%. Ten of 114 breast cancerous lesions (8.8%) were detected on prone breast PET images alone. Statistical difference was found between the sensitivity, accuracy, and NPV of prone breast PET images and those of whole-body PET images (P<0.0001 for sensitivity and accuracy and P<0.0009 for NPV). ConclusionOur data about the 122 lesions, suspected of breast cancer, with regard to the usefulness of prone breast PET imaging indicate that prone breast PET images are effective in detecting breast cancer.

The relationship between 18F-FDG metabolic volumetric parameters and clinicopathological factors of breast cancer.

ObjectivesThis study was conducted to evaluate the relationship between fluorine-18 fluorodeoxyglucose metabolic parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and clinicopathological factors of breast cancer. MethodsThe study comprised 93 patients. A volumetric region of interest was drawn over the abnormal focal uptake of breast cancer. Spearman’s rank correlation, the Kruskal–Wallis test, and receiver operating characteristic analysis were used to investigate the relationship between clinicopathological factors and metabolic parameters and determine which metabolic parameters were most highly associated with clinicopathological factors. ResultsAll parameters had a statistically significant relationship with pathological T stage (p-T stage), pathological N status (p-N status), pathological stage (p-stage), and triple-negative type (TN) (all P values were <0.05). There were statistically significant differences between SUVmax and TLG in relation to lymphatic invasion, estrogen receptor, and nuclear grade (P<0.05). High MTV showed a tendency toward association with estrogen receptor negativity, but the relation did not reach the level of statistical significance (P=0.056). No statistically significant relationship was observed between MTV and lymphatic invasion or nuclear grade. In the receiver operating characteristic analysis of p-T stage and p-stage, the AUC for TLG was significantly larger than that for SUVmax (P=0.0003 and 0.048, respectively). There were marginally significant differences between TLG and MTV in relation to p-stage (P=0.058). ConclusionTLG may reflect tumor metabolism for clinicopathological factors of breast cancer better than SUVmax or MTV.

Relationship between clinicopathological factors and fluorine-18-fluorodeoxyglucose uptake in patients with papillary thyroid cancer

ObjectiveTo examine the relationship between clinicopathological factors and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in patients with papillary thyroid cancer (PTC). Materials and methodsFifty-four patients were included in this study.18F-FDG positron emission tomography was performed before surgery. Immunohistochemistry of glucose transporter (GLUT) was performed using postoperative histopathological specimens. We investigated the relationship between maximum standardized uptake value (SUVmax) and GLUT-1, GLUT-3, and GLUT-4 expression/SUVmax and prognostic risk factors {tumor size, age, sex, extrathyroidal extension, and lymph node metastasis [ly (+)]}. ResultsGLUT-3 and GLUT-4 expressions significantly correlated with SUVmax (GLUT-3: r=0.38, P=0.008; GLUT-4: r=0.46, P=0.001), but GLUT-1 did not (r=0.21, P=0.147). The tumor size correlated with SUVmax (r=0.5, P<0.001), but GLUT-1, GLUT-3, and GLUT-4 did not (GLUT-1: r=0.006, P=0.681; GLUT-3: r=0.05, P=0.705; GLUT-4: r=−0.17, P=0.217). Both SUVmax and GLUT-4 expressions were statistically significant with ly (+) (SUVmax: P=0.012; GLUT-4: P=0.018), but GLUT-1 and GLUT-3 expressions were not (GLUT-1: P=0.165; GLUT-3: P=0.499). There was no significant difference between other clinicopathological factors and SUVmax or any GLUT expressions. Conclusion 18F-FDG uptake in PTC may be determined by GLUT-3 and GLUT-4 expressions and may be related to tumor size and lymph node metastasis of PTC. 18F-FDG uptake may reflect tumor progression of PTC.

Clinical and Biochemical Factors Associated With Area and Metabolic Activity in the Visceral and Subcutaneous Adipose Tissues by FDG-PET/CT

CONTEXT Body fat distribution and inflammation may play a role in metabolic derangements and cardiovascular disease in obesity. OBJECTIVE The aim of this study is to investigate clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues (VAT and SAT). PARTICIPANTS (18)F-fluorodeoxyglucose-positron emission tomography and computed tomography imaging was performed in 251 consecutive subjects (62.6 ± 9.3 y) for risk screening. MAIN OUTCOME MEASURES We examined which clinical, anthropometric, metabolic, and inflammatory variables including advanced glycation end products (AGEs) and pigment epithelium-derived factor (PEDF) were independently associated with area and metabolic activity in VAT and SAT. Adipose tissue area was determined with computed tomography, whereas metabolic activity was assessed by (18)F-fluorodeoxyglucose uptake expressed as a target to background ratio (TBR) of blood-normalized standardized uptake. RESULTS Serum levels of AGEs and PEDF were 9.81 ± 3.21 U/mL and 14.0 (range 10.8-17.7) μg/mL, respectively. Although the area in VAT and SAT was associated with waist circumference and sex, each adipose tissue area and TBR had different metabolic risk profiles. The TBR value in VAT was higher than that in SAT. In a multiple stepwise regression analysis, AGEs and medication for hypertension were independently associated with VAT TBR (R(2) = 0.102), whereas medication for diabetes, mean intima-media thickness, AGEs, and PEDF were the independent correlates of SAT TBR (R(2) = 0.132). CONCLUSIONS The present study demonstrated that area and metabolic activity in VAT and SAT could be differently regulated, suggesting the involvement of AGEs and PEDF in adipose tissue inflammation.

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer

Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation.Methods: Sixty patients with lung tumors, included small cell carcinoma (n=8) and non-small cell carcinoma (n=52), underwent201Tl single photon emission computed tomography (SPECT) imaging. The201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67.Results: The average201Tl index was 2.13±0.61 (early) and 2.46±0.83 (delayed). The average RI was 17.44±35.01. Overall, the201Tl index (delayed) and the cancer cell proliferation were correlated (r=0.70, p<0.0001). Of interest, there was a significant correlation (r=0.872, p<0.0005) between the201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The201Tl index (delayed) was significantly higher (p<0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma.Conclusion:201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.

Comparison between endoscopic macroscopic classification and F-18 FDG PET findings in gastric mucosa-associated lymphoid tissue lymphoma patients.

Purpose: The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. Materials and Methods: Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. Results: The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis–like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis–like tumors and 40% for depressed-type tumors. Conclusions: F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.