Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG

BACKGROUND.

The aim was to assess the relevant distribution of the novel PET tracer ⁶⁸Ga‐DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of ¹⁸F‐FDG PET/CT.

METHODS.

The imaging findings with ⁶⁸Ga‐DOTATATE and ¹⁸F‐FDG on 38 consecutive patients with a diagnosis of primary or recurrent NET were compared and correlated with tumor grade on histology based on ki67 and mitotic index.

RESULTS.

The sensitivity of ⁶⁸Ga‐DOTATATE PET/CT was 82% (31 of 38) and that of ¹⁸F‐FDG PET/CT was 66% (25 of 38). The sensitivity of combined ⁶⁸Ga‐DOTATATE and ¹⁸F‐FDG PET/CT was 92% (35 of 38). There was greater uptake of ⁶⁸Ga‐DOTATATE than ¹⁸F‐FDG in low‐grade NET (median SUV 29 vs 2.9, P < .001). In high‐grade NET there was higher uptake of ¹⁸F‐FDG over ⁶⁸Ga‐DOTATATE (median SUV 11.7 vs 4.4, P = .03). There was a significant correlation with predominant tumor uptake of ⁶⁸Ga‐DOTATATE or ¹⁸F‐FDG and tumor grade on histology (P < .0001).

CONCLUSIONS.

⁶⁸Ga‐DOTATATE PET/CT is a useful novel imaging modality for NETs and is superior to ¹⁸F‐FDG for imaging well‐differentiated NET. Functional imaging with both ⁶⁸Ga‐DOTATATE and ¹⁸F‐FDG has potential for a more comprehensive tumor assessment in intermediate‐ and high‐grade tumors. Cancer 2008. ©2008 American Cancer Society.     

Correlation of F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value and EGFR mutations in advanced lung adenocarcinoma

Objective Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are involved in the tumorigenesis and regulation of cell metabolism via Akt signaling. F-18 fluorodeoxyglucose-positron emission tomography ([¹⁸F]FDG PET), a functional imaging modality, can be used to measure tumor cell metabolism. Thus, in this study, we hypothesize that there exist correlations between EGFR mutation status and [¹⁸F]FDG uptake of advanced lung adenocarcinoma. Methods From May 2004 to April 2008, patients with stage IIIB or IV lung adenocarcinoma who underwent [¹⁸F]FDG PET and EGFR mutation analysis before receiving any treatment were eligible to participate in this study. The association of EGFR mutation status with patient characteristics and the SUV_MAX from the [¹⁸F]FDG PET was evaluated. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Results Seventy-seven lung adenocarcinoma patients were included in this study. EGFR mutations were identified in 49 (64%) of the patients. The [¹⁸F]FDG uptake was significantly higher in EGFR-mutant (mean SUV_MAX = 10.5 ± 4.7) than wild-type (8.0 ± 3.3) lung adenocarcinoma patients (P = 0.008). The median SUV_MAX was 9.5, and patients with an SUV_MAX ≥ 9.5 were more likely to harbor EGFR mutations (P = 0.009). In the multivariate analysis, an SUV_MAX ≥ 9.5 remained a statistically significant predictor of EGFR mutations (P = 0.005). Conclusions Among Asian patients with advanced lung adenocarcinoma, those with higher SUV_MAX on the [¹⁸F]FDG PET are more likely to carry EGFR mutations.     

PET/CT in breast cancer staging is useful for evaluation of axillary lymph node and distant metastases

IntroductionBreast cancer outcome is dependent on disease stage. The aim of the study was to assess the role of PET/CT in the evaluation of axillary lymph node and distant metastases in women with newly diagnosed primary breast cancer.Materials and methodsWe assessed, among patients with newly diagnosed primary breast cancer, associations of [¹⁸F] fluorodeoxyglucose (FDG) uptake (maximum standardized uptake value [SUV_max]) with clinical variables of the primary tumor, including regional nodal status and the presence of distant metastases.ResultsOf 324 patients, 265 (81.8%) had focal uptake of FDG that corresponded with the cancerous lesion, and 21 (6.5%) had no FDG-avid findings. The remaining 38 patients had diffuse or nonspecific uptake of FDG. Among patients with a focal uptake of FDG (n = 265), the mean tumor size was 2.6 ± 1.9 (range 0.5–13.5), and the mean SUV_max was 5.3 ± 4.9 (range 1.2–25.0). In 83 patients (25.6%), PET/CT demonstrated additional suspected foci in the same breast. FDG-avid lymphadenopathy was observed in 156 patients (48.1%). Further assessment of lymph node involvement was available for 55/156 patients (axillary lymph node dissection [n = 21]; core needle biopsy [n = 34]) and confirmed axillary lymph node metastases in 47 (85.5%)). Thirteen patients (4.0%) had FDG-avid supraclavicular lymph nodes and six (1.9%) had FDG-avid internal mammary lymph nodes. Distant FDG-avid lesions were detected in 33 patients (10.2%).ConclusionPET/CT is a useful diagnostic tool for staging breast cancer patients, but its use should be limited to specific clinical situations; further evaluation is needed.     

18F‐FDG uptake and its clinical relevance in primary gastric lymphoma

We studied the clinical relevance of ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty‐two patients with primary gastric lymphoma were analysed: 32 diffuse large B‐cell lymphomas (DLBCL) and 10 extranodal marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up‐staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down‐staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax ≥ median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow‐up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual ¹⁸F‐FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual ¹⁸F‐FDG uptake observed during follow‐up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd.     

Prognostic role of baseline 18F‐FDG PET/CT parameters in MALT lymphoma

Mucosa‐associated lymphoid tissue (MALT) lymphoma is an indolent lymphoma with good prognosis and variable fluorine‐18 fluorodeoxyglucose (¹⁸F‐FDG) avidity. Many possible prognostic factors have been investigated with controversial results, but the possible prognostic role of ¹⁸F‐FDG positron emission tomography/computed tomography (PET/CT) remains unclear. Our aim was to evaluate the prognostic impact of qualitative and semiquantitative baseline PET/CT parameters on outcome of MALT lymphoma. We retrospectively enrolled 161 patients with histologically confirmed MALT lymphoma who underwent ¹⁸F‐FDG PET/CT before any treatment. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The Kaplan‐Meier method was used to estimate the progression‐free survival (PFS) and overall survival (OS) times. Cox regression models were performed to determine the relation between PET/CT features and OS and PFS. Ninety‐eight patients had positive ¹⁸F‐FDG PET/CT showing ¹⁸F‐FDG uptake (mean SUVbw, 10.1; SUVlbm, 7.2; SUVbsa, 2.7; MTV, 88.8; and TLG, 526); the remaining 63 were not ¹⁸F‐FDG avid. ¹⁸F‐FDG avidity was significantly correlated with tumor size and Ki‐67 score. Relapse/progression of disease occurred in 47 patients with an average time of 40.2 months; death occurred in 12 patients with an average of 59 months. At a median follow‐up of 62 months, median PFS and OS were 52 and 62 months, respectively. Advanced tumor stage and extragastric site were demonstrated to be independent prognostic factors for PFS, while only tumor stage for OS. Instead, PET/CT parameters were not related to survival, despite positive correlation at univariate analysis between MTV and TLG with PFS and positive PET/CT with PFS and OS. In conclusion, a 61% rate of PET avidity in biopsy‐confirmed MALT lymphoma was found, and it was correlated with tumor size and Ki‐67 score. Only tumor stage and localization were independently correlated with PFS and OS.     

Metabolic tumor burden predicts prognosis of ovarian cancer patients who receive platinum‐based adjuvant chemotherapy

Volumetric parameters of positron emission tomography–computed tomography using 18F‐fludeoxyglucose (¹⁸F‐FDG PET/CT) that comprehensively reflect both metabolic activity and tumor burden are capable of predicting survival in several cancers. The aim of this study was to investigate the predictive performance of metabolic tumor burden measured by ¹⁸F‐FDG PET/CT in ovarian cancer patients who received platinum‐based adjuvant chemotherapy after cytoreductive surgery. Included in this study were 37 epithelial ovarian cancer patients. Metabolic tumor burden in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), clinical stage, histological type, residual tumor after primary cytoreductive surgery, baseline serum carbohydrate antigen 125 (CA125) level, and the maximum standardized uptake value (SUV_max) were determined, and compared for their performance in predicting progression‐free survival (PFS). Metabolic tumor volume correlated with CA125 (r = 0.547, P < 0.001), and TLG correlated with SUV_max and CA125 (SUV_max, r = 0.437, P = 0.007; CA125, r = 0.593, P < 0.001). Kaplan–Meier analysis showed a significant difference in PFS between the groups categorized by TLG (P = 0.043; log–rank test). Univariate analysis indicated that TLG was a statistically significant risk factor for poor PFS. Multivariate analysis adjusted according to the clinicopathological features was carried out for MTV, TLG, SUV_max, tumor size, and CA125. Only TLG showed a significant difference (P = 0.038), and a 3.915‐fold increase in the hazard ratio of PFS. Both MTV and TLG (especially TLG) could serve as potential surrogate biomarkers for recurrence in patients who undergo primary cytoreductive surgery followed by platinum‐based chemotherapy, and could identify patients at high risk of recurrence who need more aggressive treatment.     

Clinicopathologic Significance of False-Positive Lymph Node Status on FDG-PET in Lung Cancer

Introduction2-[¹⁸F] Fluoro-d-deoxyglucose (FDG) positron emission tomography (PET) is a relevant diagnostic procedure for staging lung cancer. However, accurate evaluation of lymph node metastases by PET is controversial because of false-positive FDG uptake.Patients and MethodsA total of 245 patients with lung cancer were retrospectively analyzed. Standardized maximum uptake values (SUV_max) of the primary tumor and lymph nodes were compared to pathologic lymph node metastases to correlate PET findings with clinicopathologic variables and patient outcomes.ResultsThe SUV_max values of metastatic lymph nodes were significantly higher than those of lymph nodes without metastases (P = .0036). When SUV_max ≥ 4 was defined as PET positive for metastasis, the sensitivity, specificity, and accuracy were 48.1%, 79.8%, and 73.1%, respectively. Multivariate logistic regression analysis showed that age > 75 years, bilateral hilar FDG uptake, and no lymph node swelling were significant factors related to false-positive lymph node metastases. Smoking status, FDG uptake in the primary tumor, and concurrent lung diseases were not significant factors.ConclusionMetastatic lymph nodes show higher FDG uptake than false-positive lymph nodes, and older patient age, bilateral hilar FDG uptake, and no swollen nodes are associated with no metastases. Patients with lymph node metastases have worse survival than those with false-positive FDG-PET findings. However, abnormal FDG uptake in the lymph node is an important prognostic factor.     

Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy

Background

Fluorine-18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine (¹¹C MET) has little uptake under normal conditions. We prospectively investigated the uptake of ¹⁸F FDG and ¹¹C MET PET in patients with craniopharyngioma prior to proton therapy.

Methods

Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using ¹⁸F FDG and ¹¹C MET. PET and MRI studies were registered to help identify tumor volume. Measurements of maximum standardized uptake value (SUV_max) were taken of the tumor and compared with noninvolved left frontal background white matter using a paired t-test. Uptake was graded using a 4-point scale.

Results

Median patient age was 9 years (range 5–19). Seven patients were diagnosed by pathology, 1 by cyst fluid aspiration, and 2 by neuroimaging. Median FDG SUV_max for tumor and background were 2.65 and 3.2, respectively. Median MET SUV_max for tumor and background were 2.2 and 1, respectively. There was a significant difference between MET tumor SUV_max and MET background SUV_max (P = .0001). The difference between FDG tumor SUV_max and FDG background SUV_max was not significant (P = .3672).

Conclusion

¹¹C MET PET uptake is significantly greater within the tumor compared with noninvolved background white matter, making it more useful than FDG PET in identifying active tumor in patients with craniopharyngioma. Future work will focus on using ¹¹C MET PET to discriminate between active and inactive tumor after irradiation.     

Axillary Lymph Node-to-Primary Tumor Standard Uptake Value Ratio on Preoperative 18F-FDG PET/CT: A Prognostic Factor for Invasive Ductal Breast Cancer

Purpose

This study assessed the axillary lymph node (ALN)-to-primary tumor maximum standard uptake value (SUV_max) ratio (ALN/T SUV ratio) in invasive ductal breast cancer (IDC) on preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to determine the effectiveness in predicting recurrence-free survival (RFS).

Methods

One hundred nineteen IDC patients (mean age, 50.5±10.5 years) with pathologically proven ALN involvement without distant metastasis and preoperative FDG PET/CT were enrolled in the study. SUV_max values of the ALN and primary tumor were obtained on FDG PET/CT, and ALN/T SUV ratio was calculated. Several factors were evaluated for their effectiveness in predicting RFS. These included several parameters on FDG PET/CT as well as several clinicopathological parameters: pathologic tumor/node stage; nuclear and histological grade; hormonal state; status with respect to human epidermal growth factor receptor 2, mindbomb E3 ubiquitin protein ligase 1 (MIB-1), and p53; primary tumor size; and ALN size.

Results

Among 119 patients with breast cancer, 17 patients (14.3%) experienced relapse during follow-up (mean follow-up, 28.4 months). The ALN/T SUV ratio of the group with disease recurrence was higher than that of the group without recurrence (0.97±1.60 and 0.45±0.40, respectively, p=0.005). Univariate analysis showed that the primary tumor SUV_max, ALN SUV_max, ALN/T SUV ratio, ALN status, nuclear and histological grade, estrogen receptor (ER) status, and MIB-1 status were predictors for RFS. Among these variables, ALN/T SUV ratio with hazard ratio of 4.20 (95% confidence interval [CI], 1.74-10.13) and ER status with hazard ratio of 4.33 (95% CI, 1.06-17.71) were predictors for RFS according to multivariate analysis (p=0.002 and p=0.042, respectively).

Conclusion

Our study demonstrated that ALN/T SUV ratio together with ER status was an independent factor for predicting relapse in IDC with metastatic ALN. ALN/T SUV ratio on preoperative FDG PET/CT may be a useful marker for selecting IDC patients that need adjunct treatment to prevent recurrence.     

High 2-[F]fluoro-2-deoxy-d-glucose (FDG) uptake measured by positron emission tomography is associated with reduced overall survival in patients with oral squamous cell carcinoma

Patients with oral squamous cell carcinoma (OSCC) and poor prognosis may benefit from an intensification of the initial therapy scheme. To improve the clinical management of these patients, there is a strong requirement for an accurate assessment of the malignant properties of the individual lesion. The objective of the present analysis was to define the potential value of 2-[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸FDG) uptake in the tumor measured by positron emission tomography (PET) in predicting patients’ outcome in the clinical course of OSCC. In this respect, a clinically well-defined cohort of 79 patients with primary OSCC was retrospectively evaluated. ¹⁸FDG uptake in the primary tumor site was quantified by calculation of the maximum standardized uptake values (SUV_max). Subsequent statistical analyses found, that ¹⁸FDG uptake of the primary tumor was significantly higher in stage T3/T4 vs. T1/T2 (p < 0.001), in UICC stage IV vs. stage I–III (p = 0.01), and in N1–3 vs. N0 tumors (p < 0.001), respectively. To define SUV_max cut-off values for survival analyses, receiver operating curves (ROC) were calculated for overall and disease-free survival after 36 and 60 months, respectively. Univariate survival analysis showed that high SUV_max was significantly associated with shortened overall survival after 36 (p = 0.026) and 60 months (p = 0.02). Subsequent multi-variate Cox regression analysis including SUV_max, age, gender and UICC stage as co-variables determined that, high SUV_max was the only predictor of inferior overall survival after 60 months (p = 0.035) in this model. In conclusion, ¹⁸FDG uptake detected by PET predicts adverse outcome of patients with OSCC in this retrospective analysis. ¹⁸FDG–PET might be a promising tool to contribute to therapeutic decisions and should be evaluated in future prospective studies.     

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

The relationship between the local immune status and cancer metabolism regarding ¹⁸F‐FDG and ¹⁸F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent ¹⁸F‐FDG PET and ¹⁸F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (¹⁸F‐FDG transporter) and LAT1 (¹⁸F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have “hot tumor immune status.” High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of ¹⁸F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of ¹⁸F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of ¹⁸F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.     

Total lesion glycolysis in oral squamous cell carcinoma as a biomarker derived from pre-operative FDG PET/CT outperforms established prognostic factors in a newly developed multivariate prediction model

Purpose: Retrospective study to investigate the impact of image derived biomarkers from [¹⁸F]FDG PET/CT prior to surgical resection in patients with initial diagnosis of oral squamous cell carcinoma (OSCC), namely SUV_max, SUV_mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor to predict overall survival (OS).Materials and Methods: 127 subsequent patients with biopsy-proven OSCC were included who underwent [¹⁸F]FDG PET/CT before surgery. SUV_max, SUV_mean, MTV and TLG of the primary tumor were measured. OS was estimated according to Kaplan-Meier and compared between median-splitted groups by the log-rank test. Prognostic parameters were analyzed by uni-/multivariate Cox-regression.Results: During follow-up 52 (41%) of the patients died. Median OS was longer for patients with lower MTV or lower TLG. SUV_max and SUV_mean failed to be significant predictors for OS. Univariate Cox-regression identified MTV, TLG, lymph node status and UICC stage as prognostic factors. By multivariate Cox-regression MTV and TLG turned out to be independent prognostic factors for OS.Conclusions: The pre-therapeutic [¹⁸F]FDG PET/CT parameters MTV and TLG in the primary tumor are prognostic for OS of patients with an initial diagnosis of OSCC. TLG is the strongest independent prognostic factor for OS and outperforms established prognostic parameters in OSCC.     

Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B‐cell lymphoma

The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F‐18] fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) treated with bendamustine–rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of ¹⁸F‐FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty‐five patients with relapsed or refractory DLBCL were enrolled. The ¹⁸F‐FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value–volume histogram was significantly greater in complete response patients than in non‐complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression‐free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression‐free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine–rituximab.     

Evaluation of thoracic tumors with 18F‐FMT and 18F‐FDG PET‐CT: A clinicopathological study

L‐[3‐¹⁸F]‐α‐methyltyrosine (¹⁸F‐FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET‐CT with ¹⁸F‐FMT provides additional information for the preoperative diagnostic workup as compared with ¹⁸F‐FDG PET. PET‐CT studies with ¹⁸F‐FMT and ¹⁸F‐FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L‐type amino acid transporter 1 (LAT1), CD98, Ki‐67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, ¹⁸F‐FMT PET exhibited a sensitivity of 84% whereas the sensitivity for ¹⁸F‐FDG PET was 89% (p = 0.736). ¹⁸F‐FMT PET‐CT and ¹⁸F‐FDG PET‐CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). ¹⁸F‐FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of ¹⁸F‐FMT PET for diagnosing thoracic tumors was higher than that of ¹⁸F‐FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer. © 2008 Wiley‐Liss, Inc.     

Prognostic value of 18F‐fluoroazomycin arabinoside PET/CT in patients with advanced non‐small‐cell lung cancer

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using ¹⁸F‐fluoroazomycin arabinoside (FAZA) in patients with advanced non‐small‐cell lung cancer (NSCLC) compared with ¹⁸F‐fluorodeoxyglucose (FDG). Thirty‐eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor‐to‐muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression‐free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy‐treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.     

Gastric cancers with microsatellite instability exhibit high fluorodeoxyglucose uptake on positron emission tomography

Background

Gastric cancers exhibit various degrees of ¹⁸F-fluorodeoxyglucose (FDG) uptakes on positron emission tomography/computed tomography (PET/CT) imaging. The aim of this study was to evaluate whether FDG uptake in gastric cancer varies according to the microsatellite instability (MSI) status.

Methods

Consecutive gastric cancer patients who underwent PET/CT imaging and MSI analysis were included in the study. The maximum standardized uptake value (SUV_max) of gastric cancer was assessed using PET/CT imaging.

Results

Of 131 gastric cancers, 16 exhibited a high incidence of MSI (MSI-H) and 3 exhibited a low incidence of MSI (MSI-L). In 29 subjects who showed no uptake on PET/CT imaging the gastric cancers were all microsatellite stable (MSS). Gastric cancers with MSI were related to age older than 60 years (p = 0.002), cancer volume larger than 10 cm³ (p = 0.015), and the presence of FDG uptake on PET/CT imaging (p = 0.001). A higher SUV_max of gastric cancer was linked to the presence of MSI (p < 0.001).

Conclusion

The presence of MSI is related to FDG uptake in gastric cancer. Care should be taken with MSS gastric cancers, because they show lower SUV_max on PET/CT imaging than MSI gastric cancers.     

Prognostic value of 18FDG PET/CT volumetric parameters in the survival prediction of patients with pancreatic cancer

PurposeTo investigate the value of ¹⁸ FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables.MethodsWe conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent ¹⁸ FDG PET/CT. The tumour maximum standardised uptake value (SUV_max) in addition to SUV_mean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of ¹⁸ FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses.ResultsA sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUV_mean, MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUV_max, SUV_mean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26–3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97–5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis.Conclusions¹⁸ FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings.     

Comparison of magnetic resonance spectroscopy and positron emission tomography in detection of tumor recurrence in posttreatment of glioma: A diagnostic meta‐analysis

It is important to distinguish between tumor recurrence and treatment effects in posttreatment patients with high‐grade gliomas. Several imaging modalities have been reported in differentiating between tumor recurrence and treatment effects. However, there were no consistent conclusions between different studies. We performed a meta‐analysis of 23 studies that compared the diagnostic values of fluorine‐18‐fluorodeoxyglucose (¹⁸F‐FDG) and ¹¹C‐methionine (¹¹C‐MET) PET (positron emission tomography) or PET/CT (computed tomography) and magnetic resonance spectroscopy (MRS) in predicting tumor recurrence of gliomas. The pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and summary receiver operating characteristic curves of ¹⁸F‐FDG and ¹¹C‐MET PET or PET/CT and MRS in detecting tumor recurrence were calculated. In conclusion, MRS is highly sensitive in the detection of tumor recurrence in glioma.¹⁸F‐FDG PET or PET/CT is highly specific in recurrence diagnosis. ¹¹C‐MET does not have noticeable advantage over ¹⁸F‐FDG. The current evidence shows no statistical difference between MRS and PET on the accuracy.     

Cervical cancer histology and tumor differentiation affect 18F‐fluorodeoxyglucose uptake

BACKGROUND:

This study aimed to evaluate the variation in cervical cancer glucose metabolism for different tumor histologies and levels of differentiation, as measured by the uptake of ¹⁸F‐fluorodeoxyglucose (FDG) by positron emission tomography (PET).

METHODS:

The study population consisted of 240 patients with International Federation of Gynecology and Obstetrics stages Ib1 through IVb cervical cancer, who underwent a pretreatment FDG‐PET. Tumor histology included 221 squamous cell (SC), 4 adenosquamous (AS), and 15 adenocarcinoma (AC) tumors. There were 14 well, 145 moderately, and 81 poorly differentiated tumors. The stage distribution was as follows: 70 stage I tumors (9 AC, 2 AS, and 59 SC), 102 stage II tumors (3 AC, 1 AS, and 98 SC), 64 stage III tumors (3 AC, 1 AS, and 60 SC), and 4 stage IV tumors (4 SC). From the FDG‐PET, maximal standardized uptake value (SUV_max) was determined. The variation in SUV_max was analyzed for differences based on tumor histology and differentiation.

RESULTS:

For all patients, the mean SUV_max was 11.62 (range, 2.50‐50.39). The mean SUV_max by histology was as follows: SC, 11.91 (range, 2.50‐50.39); AS, 8.85 (range, 6.53‐11.26); and AC, 8.05 (range, 2.83‐13.92). Squamous versus nonsquamous tumors demonstrated a significant difference in SUV_max (P = .0153). SUV_max and tumor volume were not found to be correlated (R² = 0.013). The mean SUV_max was 8.58 for well‐differentiated, 11.56 for moderately differentiated, and 12.23 for poorly differentiated tumors. The mean SUV_max was significantly different for well?differentiated versus poorly differentiated cervical tumors (P = .0474).

CONCLUSIONS:

Cervical tumor FDG uptake varied by histology and differentiation. SC tumors demonstrated a significantly higher SUV_max compared with nonsquamous cell tumors, and poorly differentiated tumors also had a higher SUV_max. Cancer 2009. © 2009 American Cancer Society.     

Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non–small‐cell lung cancer patients

In the recent years, fluorine 18 fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography (PET)/computed tomography (CT) has emerged as a new modality for staging non–small‐cell lung cancer (NSCLC) patients. The aim of this meta‐analysis was to assess the diagnostic value of ¹⁸F‐FDG PET/CT in detecting metastatic lesions in NSCLC patients. Meta‐analysis methods were used to pool sensitivity, specificity, positive and negative likehood ratios, diagnostic odd ratios and to construct a summary receiver‐operating characteristic curve. Data from included studies were pooled to compare the diagnostic accuracy between PET/CT and PET or CT alone in nodal staging. Totally, 56 studies involving 8,699 patients met the inclusion criteria. The pooled sensitivities and specificities of ¹⁸F‐FDG PET/CT were 0.72 [95% confidence interval (CI): 0.65–0.78] and 0.91 (95% CI: 0.86–0.94) in determining mediastinal nodal staging; 0.71 (95% CI: 0.60–0.80) and 0.83 (95% CI: 0.77–0.88) in intrathoracic staging; 0.78 (95% CI: 0.64–0.87) and 0.90 (95% CI: 0.84–0.94) in intrathoracic staging on a per‐node basis. For detecting extrathoracic metastases, the pooled sensitivities and specificities of ¹⁸F‐FDG PET/CT were 0.77 (95% CI: 0.47–0.93) and 0.95 (95% CI: 0.92–0.97) for all extrathoracic metastases; 0.91 (95% CI: 0.80–0.97) and 0.98 (95% CI: 0.94–0.99) for bone metastases. ¹⁸F‐FDG PET/CT is beneficial in detecting lymph node metastases and extrathoracic metastases although PET/CT showed low sensitivity in detecting brain metastases. ¹⁸F‐FDG PET/CT confers significantly higher sensitivity and specificity than contrast‐enhanced CT (both p < 0.01) and higher sensitivity than ¹⁸F‐FDG PET in staging NSCLC (p < 0.05).