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PURPOSE This study aimed to evaluate the diagnostic value of a support vector machine (SVM) model built with texture features based on standard 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) PET in patients with solitary pulmonary nodules (SPNs) at a volume larger than 5 mL. PATIENTS AND METHODS The PET results of 82 patients diagnosed with SPNs between 2014 and 2018 were retrospectively analysed. The volumes of interest (VOIs) of the SPNs were automatically segmented using threshold techniques from the standard PET imaging. Then, a large number of texture features were extracted from the VOIs using texture-analysis software. Next, an optimized SVM machine-learning model that was trained on standard PET images using texture features was employed to identify the optimal discrimination between malignant and benign nodules. Diagnostic models based on the maximum standardized uptake value (SUVmax) and the metabolic tumour volume (MTV) were compared with the SVM model with regard to the SPN diagnostic power. RESULTS Compared with the SUVmax and MTV models, the texture-based SVM model provided an improvement of approximately 20% in diagnostic accuracy, positive predictive value, negative predictive value and the area under the operating characteristic curve. The receiver operating characteristic curve of the SVM model showed a significant improvement compared with the MTV model (P = 0.0345

Objective To compare the predictive value of European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST), for the pathological response and prognosis of patients with breast cancer receiving neoadjuvant chemotherapy (NAC). Methods Consecutive PET/computed tomography scans in 128 operable female patients at baseline and after two courses of NAC were performed. Patients were categorized by complete metabolic response (CMR) and non-CMR groups using 2 PET criteria. CMR and non-CMR were used to predict pathological complete response (pCR) by diagnostic test evaluation, and to predict progression-free survival (PFS) using Kaplan-Meier plots and Cox proportional hazards regression. Results Ninety-two patients were finally analyzed. The sensitivity, specificity, and accuracy for pCR prediction were 69.7, 76.3, and 73.9% with EORTC criteria, and 69.7, 77.9, and 75.0% with PERCIST, respectively. Peak standardized uptake value normalized to lean body mass (SULpeak), maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were pCR response with accuracy of 70.7, 60.0, 75.0, and 71.4%, respectively. CMR by the EORTC (P = 0.021) and PERCIST (P = 0.007) was significantly related to a longer PFS. The univariate and multivariate analysis suggested that CMR by PERCIST was an independent predictor of recurrence (P = 0.008). Conclusion EORTC criteria and PERCIST had early predictive value to long-term outcome, but moderate value for pCR. Furthermore, PERCIST might show more potential than the EORTC criteria and conventional PET-based parameters to predict prognosis in breast cancer patients following two cycles of neoadjuvant chemotherapy.Video abstract: see http://links.lww.com/NMC/A162.

Objective Our purpose is to investigate whether the tumor uptake of Tc-HYNIC-TOC in patients with neuroendocrine tumor would be influenced when the patients were treated with long-acting octreotide. Methods Sixty G2 neuroendocrine tumor patients who underwent Tc-HYNIC-TOC single-photon emission computed tomography/computed tomography imaging were retrospectively analyzed. The ratios of target/muscle of normal organs and tumors were compared between the patients with (n = 30) and without octreotide treatment (n = 30). In addition, the octreotide treatment group was divided into two subgroups based on whether the time intervals were more than 14 days between the last time of octreotide administration and the day of imaging. Results There was no statistical significance in target/muscle of primary tumors (23.86 ± 4.49 vs. 20.72 ± 5.37, P = 0.070), metastases in the liver (20.74 ± 6.14 vs. 19.72 ± 6.54, P = 0.211), lymph nodes (16.29 ± 9.45 vs. 15.52 ± 7.67, P = 0.867), bone (9.18 ± 3.83 vs. 9.07 ± 3.61, P = 0.989) and lung (16.99 ± 6.06 vs. 12.40 ± 5.97, P = 0.133) between octreotide treated and untreated group. However, target/muscle of normal liver and bone were lower in the octreotide treated group than in untreated group (P = 0.003, and 0.0001, respectively). There was also no significant difference in target/muscle of normal organs, primary tumors and metastases between the two subgroups. Conclusion Octreotide treatment had no impact on the results of Tc-HYNIC-TOC single-photon emission computed tomography/computed tomography to detect tumors and metastasis in patients with neuroendocrine tumor. However, the uptake in normal liver and bone can be reduced, which might increase the detection rate of lesions in corresponding organs.

Purpose: How the neddylation pathway functions in breast tumor and regulation of estrogen receptor (ER) expression is rarely reported. The purpose of this study was to identify the role of neddylation in breast cancer and ER expression, and further explore the underlying mechanisms. Experimental Design: Expression patterns of nedd8-activating enzyme (NAE) and nedd8, two key proteins in the neddylation pathway, were examined in human breast specimens. ER-α expression was investigated using animal 18F-FES-PET/CT and immunoblotting upon NAE inhibitor MLN4924 treatment. Chromatin immunoprecipitation assay, luciferase reporter promoter assay, and the CRISPR-Cas9 system were used to elucidate the mechanism of ER-α regulation by MLN4924. The ER-positive breast cancer mouse model was used to determine the synergetic effect of MLN4924 and fulvestrant on tumor growth. All statistical tests were two-sided. Results: Both NAE1 and nedd8 expressions were higher in the ER-positive subgroup. Higher expressions of NAE1 and nedd8 indicated poorer prognosis. Importantly, ER-α expression was significantly downregulated upon MLN4924 treatment in vitro and in vivo. Mechanistically, MLN4924 treatment delayed serum and glucocorticoid-induced protein kinase (SGK) degradation and induced Forkhead box O3a (FOXO3a) nuclear export as well as decreased binding to the ESR1 promoter. Importantly, MLN4924 single or synergized with fulvestrant significantly suppressed the growth of ER-positive breast cancer in vitro and in vivo. Conclusions: Our proof-of-principle study determines the activation of neddylation in breast tumor tissues for the first time and reveals a new ER-α regulatory mechanism, as well as further explores an effective approach to improve fulvestrant sensitivity through a neddylation inactivation combination.

Background Sentinel lymph node is the first stop of lymphatic spreading of cancer with known primary. The lymph node metastasis pattern of cancer of unknown primary (CUP) is unclear and has been presumed to follow the same pathway. To test this hypothesis, data of all 716 patients clinically diagnosed as CUP in our center were collected. Methods Diagnoses of lymph node metastasis were established by 18F-FDG PET-CT and/or biopsy pathology. Three hundred and forty-seven cases meeting the criteria were divided into three groups: pathology-confirmed primary with invasive biopsy or surgery of the suspicious lesion (group A, n = 64), primary still unknown even with invasive biopsy or surgery of the suspicious lesion (group B, n = 204), and others with no suspicious lesion or lesions who had not been sampled due to medical or other reasons (group C, n = 79). We assessed the clinicopathological features between these groups, and the relationship between lymph node metastasis pattern and confirmed primary site. Results In group A, the primary sites of 61 cases were compatible with sentinel node theory, resulting in a positive predictive value of 95%. No significant differences in age, sex, bone metastasis, or visceral metastasis observed between group A and group B, except that group A had a higher ratio of differentiated carcinoma (94% vs. 77%, P = 0.003). Conclusion To our knowledge, this is the first evidence indicating that the majority of clinical CUP cases follow the sentinel node theory to spread in lymph nodes, which helps tracking the primary, especially for differentiated carcinoma.

Stroke and fine particulate matter (PM

Background Not a large number of previous studies have reported the normal sagittal balance of the cervical spine and physiological cervical lordosis (CL) has not been clearly defined yet. Methods This was a prospective radiological analysis of asymptomatic subjects. The following cervical sagittal parameters were measured: CL, thoracic inlet angle (TIA), T1 slope (T1S), neck tilt (NT), and C2–7 sagittal vertical axis (C2–7 SVA). The Pearson correlation test was calculated, and the stepwise multiple regression analysis was conducted by using the CL (dependent variable) and the other cervical sagittal parameters (independent variables) to determine the best sets of predictors. A paired sample t test was conducted between the predicted and measured values. Results The mean age of 307 participants was 24.54 + 3.07. The mean CL, TIA, T1S, NT, and C2–C7 SVA was 17.11° ± 6.31°, 67.87° ± 7.78°, 25.84° ± 5.36°, 42.53° ± 6.68°, and 14.60 ± 8.20 mm, respectively. The formula was established as follows: CL = 0.762 × T1S − 0.392 × C2–C7 SVA + 0.25 × TIA − 13.795 (R = 0.812, R2 = 0.660) (stepwise multiple regression) and CL = 0.417 × TIA − 11.193 (R = 0.514, R2 = 0.264) (simple linear regression). There was no statistical difference between the predicted CL and the measured CL (t = 0.034, P = 0.973). Conclusions There was a significant correlation between CL and other cervical sagittal parameters, including TIA, T1S, NT, and C2–C7 SVA in asymptomatic Chinese population. The results of this study may serve as a normal reference value for the study of asymptomatic population.

The present explorative study was initiated to evaluate the clinical value of 18F-FES PET/CT in monitoring the change of estrogen receptor (ER) expression and potential predictive value in metastatic breast cancer patients. Twenty-two pathology-confirmed breast cancer patients were prospectively enrolled and randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel + fulvestrant, n = 8). The percentage of patients without disease progression after 12 months (PFS > 12 months) was 62.5% in group TF compared with 21.4% in group T (P = 0.08). According to 18F-FES PET/CT scans, the SUVmax (maximum standard uptake value) of all the metastatic lesions decreased in group TF after 2 cycles of treatment (6 weeks ± 3 days). However, 6 of 9 patients in group T had at least one lesion with higher post-treatment SUVmax. There was a significant difference in the reduction of ER expression between these two groups (P = 0.028). In group TF, the patients with PFS > 12 months had significantly greater SUVmax changes of 18F-FES than those with PFS 12 months: 91.0 ± 12.0% versus PFS t = −4.64, P = 0.01). Our preliminary study showed that 18F-FES PET/CT, as a noninvasive method to monitor ER expression, could be utilized to predict prognosis based on changes in SUVmax.

Introduction The aim of our study was to investigate the effect of a 'virtual experience' on reducing people's anxiety levels and improving image quality. Methods This study included 200 people who underwent 18 F-FDG PET/CT scan for the first time. Healthy people (n = 100) and patients (n = 100) were randomly divided into a control group and an intervention group. In the intervention group, we used a 'virtual experience' as an intervention before the scan. We used the Spielberger State-Trait Anxiety Inventory (STAI) and satisfaction questionnaires for evaluation. Additionally, the image quality was analysed. Results In the control group, more patients presented anxiety than healthy people (26(52%) versus 15(30%)) (P = 0.041). However, when the 'virtual experience' was provided, the number of cases of anxiety in the patient group decreased to 19(38%). Furthermore, patients in the intervention group had lower STAI-related scores than those in the control group (STAI-S: 37.08 ± 9.42 versus 43.34 ± 10.49, P = 0.109; STAI-T: 36.24 ± 9.55 versus 40.72 ± 9.00, P = 0.019). With respect to image quality, people who had higher STAI-related scores were more likely to have unqualified images. Conclusion A 'virtual experience' provided by an audio-visual installation can ease patients' anxiety and improve image quality.

OBJECTIVES Extensive skeletal muscle accumulation (ESMA) of F-FDG adversely affects the visual interpretation of F-FDG PET/computed tomography (CT) images. We mainly investigated factors related to ESMA that are based on food compositions. METHODS From January 2018 to June 2018, a total of 5554 patients underwent F-FDG PET/CT imaging with at least a 4-hour fast. Among them, 49 patients who exhibiting ESMA and 50 sex-matched and age-matched patients without ESMA were included in the study. The following factors were analysed: BMI, plasma glucose, gastric residue, the total energy of food the patient had before F-FDG injection and the percentages of the food ingredients. Multivariate analysis was performed to evaluate related risk factors between two groups. RESULTS In brief, 49 cases and 50 controls were identified. The BMI, gross energy, gross energy of protein, gross energy of carbohydrate and proportion of protein of case group were not significantly different from that of the controls (P ≥ 0.05). The plasma glucose was significantly higher in the case group than in the control group (P = 0.002). The positivity of gastric food residue would more easily demonstrate ESMA than those without gastric food residue (P < 0.0001). The fasting time before scan, gross energy of fat, proportion of fat and proportion of carbohydrate in case group were significantly different with control group. After multivariate analysis, fasting time, gastric food residue and proportion of carbohydrate were investigated as independent risk factors. CONCLUSION To avoid ESMA, patients should take a lower proportion of carbohydrate before receiving an F-FDG administration.

BACKGROUND: The aim of this study was to investigate the predictive value of early changes in (18)F‐fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)‐positive metastatic breast cancer. MATERIALS AND METHODS: Patients underwent (18)F‐FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1‐SUVmax on scan 2)/ SUVmax on scan 1] * 100%. RESULTS: In total, 294 (18)F‐FES‐positive lesions from 36 patients were identified. The (18)F‐FES SUVmax varied widely among lesions (median 5.7; range 1.8–32.4) and patients (median 5.1; range 2.5–13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from −5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression‐free survival (PFS) than those with ΔSUVmax

Endocrine monotherapy of breast cancers is generally hampered by the primary/acquired resistance and adverse sides in clinical settings. Herein, advantaging the multitargeting antitumor effects and normal organ-protecting roles of Chinese herbal medicine, the aim of this study was to investigate the enhanced synergistic efficacy of fulvestrant plus Tan IIA combination therapy in ER-positive breast cancers and to monitor the early response by longitudinal 18F-FES PET/CT imaging. The experimental results showed FUL + Tan IIA combination therapy significantly inhibited tumor growth of ER-positive ZR-75-1 tumor xenografts and exhibited distinct antitumor effects at an earlier time point after treatment than did the monotherapy of FUL or Tan IIA. Moreover, 18F-FES PET/CT imaging competently monitored the early response of FUL + Tan IIA combination therapy. The quantitative 18F-FES %ID/gmax in vivo was further confirmed by and correlated well with ERα expression ex vivo. In conclusion, the synergic effect of FUL + Tan IIA combination therapy to ER-positive breast cancers was verified in the preclinical tumor models and the early treatment response could be monitored by 18F-FES PET/CT.

Aim To investigate apparent diffusion coefficient (ADC) as a prognostic indicator in primary central nervous system lymphoma (PCNSL) by analysing patient clinical characteristics and pretherapeutic diffusion-weighted imaging (DWI). Materials and methods Clinical characteristics and pretherapeutic DWI were studied retrospectively in 28 patients receiving high-dose methotrexate (HD-MTX)-based chemotherapy. Mean (ADC mean ), 95th percentile (ADC 95% ), and 5th percentile (ADC 5% ) ADC values of the enhancing tumour volume were measured. The influence of prognostic parameters on progression-free survival (PFS) was investigated by log-rank test and Cox regression analysis. Correlations between the variables and PFS or the level of Ki-67 expression were analysed. ADC and clinical features were analysed using an independent sample t -test between the complete response (CR i ) and partial response (PR i ) groups after initial four cycles of chemotherapy. Receiver operating characteristic (ROC) curves were constructed using ADC parameters. Results Patients with CR i , lower Ki-67 level, higher Karnofsky performance status (KPS), ADC 5% , or ADC mean showed better PFS. The level of Ki-67 expression and ADC 5% were independent risk factors. There was a positive correlation between KPS, ADC 5% , and PFS, and negative correlation between ADC 5% , PFS, and the level of Ki-67 expression. There was a significant difference for PFS, KPS, ADC mean , and ADC 5% between CR i and non-CR i ; however, ADC 5% outperformed ADC mean because the area under the ROC curve (AUC) using ADC 5% (0.983) was higher than the AUC using ADC mean (0.822). Conclusion ADC measurements, especially ADC 5% , are useful predictors for PFS and response to HD-MTX in PCNSL.

Background Thresholds for using Preoperative Systemic Therapy (PreST) have decreased to include early breast cancer. This study investigates the predictive value of axillary lymph node (ALN) status before and after systemic therapy and discusses whether it is better to receive PreST first in operable HER2-overexpressing breast cancer patients. Methods From January 2008 to June 2013 at Fudan University Shanghai Cancer Center, we identified 406 eligible female patients with stage II-IIIa, operable and pathologically confirmed HER2-overexpressing invasive ductal carcinoma. Of these patients, 269 underwent surgery first followed by chemotherapy plus trastuzumab (chemo-trastuzumab) (SurgFirst group), whereas 137 received systemic chemo-trastuzumab therapy first followed by surgery (STFirst group). Disease-free survival (DFS) and overall survival (OS) were evaluated according to different ALN statuses using the Kaplan–Meier method. Multivariate COX model analyses were also conducted. Results The median follow-up time was 47 months (IQR: 37–60). Both ALN status and overall pathological complete remission (pCR) status were shown to be significant for the prediction of DFS ( p = 0.001 and p = 0.005, respectively) and OS ( p = 0.009 and p = 0.027, respectively) in the STFirst group. However, patients with positive ALN(s) did not experience significantly poorer survival compared with those with negative ALN in the SurgFirst group. The adjusted hazard ratios (HRs) for positive ALN status in the STFirst and SurgFirst groups were 6.66 ( p = 0.001, 95%CI: 2.18–20.38) and 2.40 ( p = 0.126, 95%CI: 0.78–7.34), respectively. Conclusion The ALN status after systemic chemo-trastuzumab therapy better predicts the survival outcome. We recommend the application of PreST followed by surgery in patients with operable HER2-overexpressing breast cancer.

Purpose: To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer. Experimental Design: A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis. Results: For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P = 0.134) and disease control (AUC = 0.66; P = 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P = 0.010) and disease control status (P = 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P = 0.004). Conclusions: Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration. Clin Cancer Res; 22(7); 1603–10. ©2015 AACR.

Apoptosis may be an indication of success therapy, and precise detection of apoptosis can provide instructional suggestions in the therapy management of malignant tumors.We used CNE-1 cell lines for in vitro experiments, and colony formation assay, CCK-8 assay, cell apoptosis analysis, and western blotting were performed. For in vivo experiments, subcutaneous xenotransplanted tumor models of CNE-1 in nude mice were established. Then, small animal positron emission tomography/X-ray computed tomography (PET/CT) images were acquired by tail intravenous injection of 2-(5-[In the presence of Cetuximab, the number of colonies of CNE-1 cells decreased significantly after irradiation at 1 and 2 Gy. In addition, Cetuximab increased the radiation-induced cytotoxicity and apoptosis of CNE-1 cells. Mechanistic studies demonstrated that Cetuximab enhanced radiosensitivity by suppressing the EGFR/PI3-K/AKT pathway. In PET/CT imaging, the tumors showed clear uptake of [Our work revealed that Cetuximab could increase the radiosensitivity of CNE-1 cells both in vitro and in vivo. Apoptosis imaging with [

Background Intratumoral heterogeneity of 18F-fluorodeoxyglucose (18F-FDG) uptake in primary tumor has proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intraindividual heterogeneity in metastatic diseases remains unknown. The aim of this study was to evaluate pretreatment positron emission tomography/computed tomography (PET/CT) 18F-FDG-based heterogeneity for the prediction of first-line treatment outcome in metastatic triple-negative breast cancer (mTNBC). Materials and Methods mTNBC patients from three clinical trials (NCT00601159, NCT01287624, and NCT02341911) with whole-body 18F-FDG PET/CT scan before first-line gemcitabine/platinum were included. Heterogeneity index (HI) and the maximum of FDG uptake (MAX) across total metastatic lesions (-T) on baseline PET/CT scans were assessed. HI was measured by MAX divided by the minimum FDG uptake across metastatic lesions. Optimal cutoffs were determined by time-dependent receiver operator characteristics (ROC) analysis. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results A total of 42 mTNBC patients were included in this study. The median PFS of patients with high HI-T (>1.9) and high MAX-T (>10.5) was significantly shorter than patients with low HI-T ( Conclusion HI and MAX measured among metastatic lesions on pretreatment 18F-FDG PET/CT scans could be potential predicators for first-line treatment outcome in patients with mTNBC. Implications for Practice Intratumoral heterogeneity of 18F-fluorodeoxyglucose (FDG) uptake in primary tumor has proven to be a robust surrogate predictive marker. A novel positron emission tomography/computed tomography (PET/CT) parameter-heterogeneity index (HI) to quantify the heterogeneous characteristics of metastatic disease is proposed. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and remains a clinical challenge. The predictive performance of HI, along with the maximum FDG uptake (MAX), measured on pretreatment PET/CT scans in patients with metastatic TNBC was evaluated. Results indicate that HI and MAX may serve as applicable imaging predicators for treatment outcome of metastatic TNBC in clinical practice.

OBJECTIVE The aim of this study was to explore the clinical and prognostic implication of preoperative fluorine-18-fluorodeoxyglucose uptake value of omental metastasis-related in advanced high-grade serous ovarian cancer patients (HGSC). PATIENTS AND METHODS We retrospectively investigated HGSC patients with omental metastasis (International Federation of Gynecology and Obstetrics stage IIIB-IV) who underwent PET/CT before primary surgery in our hospital between January 2010 and January 2016. All patients were confirmed omental metastasis by postoperative pathology. None of these patients received neoadjuvant chemotherapy. PET/CT parameters, including maximum standardized uptake value of primary ovary tumor (SUVp), omental metastasis (SUVo), and omental metastasis-to-primary tumor (SUVo/p) were measured. The relationships between PET/CT parameters and clinical characteristics were analyzed by t-test. Kaplan-Meier methods and log-rank tests were used to analyze progression-free survival (PFS) in univariate analysis. For multivariate analysis, COX regression analysis was used to assess the prognostic predictive value of PET/CT-derived variables. RESULTS Totally 81 advanced HGSC patients with omental metastasis were enrolled in our study, and 49 (60.5%) patients experienced recurrence and disease progression. The median (range) follow-up time was 18.5 (7-72) months. Older patients showed higher level of SUVo/p (P=0.006). Chemosensitive patients had lower levels of SUVo (P=0.009) and SUVo/p (P

Nanomedicine has significantly impacted cancer theranostics. However, its efficiency is restricted by the limited enhanced permeability and retention effect of nanomaterials and insufficient density/specificity of receptors of tumor cells. Herein, an apoptosis-homing nanoplatform based on zinc(II) dipicolylamine (ZnDPA) conjugated Fe/Fe3 O4 nanoparticles (MNPs/ZnDPA), which demonstrates amplified magnetic resonance signal and photothermal therapy, is developed. In an apoptotic xenograft model constructed by doxorubicin, due to the high affinity between ZnDPA and the upregulated level of phosphatidylserine on the outer surface of apoptotic cancer cells, the accumulation value of MNPs/ZnDPA is enhanced two-fold and the tumor/muscle ratio of T2 values is decreased to 50% compared to that in the normal xenograft model. In the apoptotic xenograft model, the amplifying photothermal therapy is confirmed by the changes of the relative tumor volume and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. This nanoplatform provides a promising strategy to improve the targeting efficiency of nanoparticles and the enhancement of tumor-targeting theranostics.

Our aim of this research was to determine the value of SPECT/CT withWe retrospectively analyzed 184 patients who performedIn group 1, 95/140 (67.9%) patients were confirmed as neuroendocrine neoplasms including 85 neuroendocrine tumors and 10 neuroendocrine carcinomas. Patient-based analysis showed that the sensitivity, specificity and accuracy of diagnosing neuroendocrine neoplasms with SPECT/CT were 81.1, 84.4 and 82.1%. There was significant difference of TBRs among G1, G2 and G3 (F = 3.175, P = 0.048). In group 2, 22/44 (50.0%) patients occurred metastasis mainly in liver. The sensitivity, specificity and accuracy of monitoring recurrence were 87.0, 100 and 93.2%.

Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu

Heterogeneity has been demonstrated to be a predictor of treatment failure and drug resistance. Our study aimed to investigate imaging parameters, including tumor heterogeneity, as prognostic factors of response to 500 mg fulvestrant using 18F-FDG PET/CT. Twenty-seven estrogen receptor (HR)-positive/HER2-negative metastatic breast cancer patients who received 500 mg fulvestrant and underwent 18F-FDG PET/CT before treatment were retrospectively included. In PET/CT scans, conventional parameters (maximum and mean standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and heterogeneity parameters (intra-tumor heterogeneity index [HI] and inter-tumor heterogeneity coefficient of variation [COV]) were analyzed. Progression-free survival (PFS) was mainly assessed for efficacy. The survival analyses were performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard model. Univariate analysis indicated that a high SUVmax and a high tumor HI at baseline were associated with longer PFS of fulvestrant (P = 0.036 and P = 0.033, respectively). Liver metastasis, SUVmax and HI were statistically significant in multivariate analysis (P values of 0.017, 0.025 and 0.043, respectively). 18F-FDG based intra-tumor heterogeneity appears to be a potential predicator of efficacy of fulvestrant among HR+HER2− metastatic breast cancer patients.

Our study aimed to investigate the feasibility of PET/CT for monitoring the influence of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer.Docetaxel-insensitive ERα+ breast cancer cells (DIS-ZR751) were established, identified and cultured. ERα expression, toxicity and viability of DIS-ZR751 were analyzed before and after treatment in vitro. DIS-ZR751-bearing nude mice were randomly divided into four groups according to different treatments: blank (DIS-ZR751), docetaxel (DIS-ZR751+DOC), fulvestrant (DIS-ZR751+FUL), and combination treatment (DIS-ZR751+DOC+FUL).ERα expression level and growth rate of DIS-ZR751 were higher than control group and decreased dramatically after docetaxel and fulvestrant combination treatment.

The aim of this prospective study was to assess the ability of 18F-fluorodeoxyglucose ((18)FDG) positron emission tomography/computed tomography (PET/CT) scanning to predict pathological complete response (pCR) in breast cancer, and to investigate whether timing of the scan and trastuzumab treatment influence the accuracy of pCR prediction in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We treated 81 locally advanced breast cancer patients with four cycles of neoadjuvant chemotherapy (NAC). HER2-negative breast cancer patients received NAC alone, while HER2-positive breast cancer patients received NAC plus trastuzumab. (18)FDG PET/CT scans were scheduled at baseline and after the second cycle of NAC. Axillary lymph node (ALN) dissection was performed after the last cycle of neoadjuvant therapy. Relative changes in standardized uptake values (SUV) between the two PET/CT scans (ΔSUV) in primary tumors and ALN metastases were calculated. There were 75 patients with 150 PET/CT scans in the final analysis, including 41 HER2-negative and 34 HER2-positive cases. In the HER2-negative group, the ΔSUV predicted overall and ALN pCR; the receiver operating characteristics-areas under curve (ROC-AUC) were 0.87 and 0.80 (P = 0.0014 and 0.031, respectively) and the negative predictive values were 94% and 89% respectively. However, in the HER2-positive group, ΔSUV could predict neither overall nor ALN pCR; the ROC-AUCs were only 0.56 and 0.53, with P = 0.53 and 0.84, respectively. Hence, the ΔSUV after two cycles of neoadjuvant therapy could predict pCR in HER2-negative patients treated with NAC alone, but not in HER2-positive patients treated with NAC plus trastuzumab.

Aim To evaluate the efficacy of combined PET/CT in the detection of viable tumour in patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The correlation between 2-[18F]-fluoro-2-deoxy- d -glucose (FDG) uptake during PET and prognosis was evaluated. Materials and methods Seventy-three patients with 91 HCCs who had undergone TACE with lipiodol before 18F-FDG PET/CT were retrospectively reviewed. The pattern of lipiodol deposition in the tumour was divided into three groups: grade I, lipiodol remaining in ≥60% of the tumour; grade II, 20–60%; and grade III, ≤20%. The performance of 18F-FDG PET/CT in evaluating the viability of HCC was assessed and compared with that of contrast-enhanced CT (CECT). The predictive value of maximal tumoural standardized uptake value (SUV) to mean liver SUV (TSUVmax/LSUVmean) ratio was tested. Results Comparing the receiver-operating characteristic area, 18F-FDG-PET/CT was found to be superior to CECT for the detection of viable tumour in patients with HCC after TACE (p = 0.04). A high SUV ratio (TSUVmax/LSUVmean ≥1.65) correlated significantly with tumour size (p = 0.0096), the grade of lipiodol deposition (p = 0.0387) and serum α-foetoprotein (AFP) level (p = 0.0142), but did not correlate with pathological grade (p = 0.2626). The overall survival rate was significantly higher in the low SUV ratio (TSUVmax/LSUVmean Conclusion 18F-FDG-PET/CT is efficient in assessing the viability of HCC after TACE and is superior to CECT in grades I and II, and similar in grade III. It provides valuable information for prediction of prognosis and may aid decisions regarding treatment strategy.

This study was designed to evaluate the utility of textural features for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC).Sixty-one consecutive patients with locally advanced breast cancer underwentpCR was observed more often in patients with HER2-positive tumors (22 patients) than in patients with HER2-negative tumors (5 patients) (71.0 vs. 16.7%, p 0.001). ∆ %SUVThe early changes in the textural features of

The aim of this study was to investigate the clinical value of F-fluoroestradiol (F-FES) PET/CT in the assessment of the estrogen receptor (ER) and its intratumoral heterogeneity in breast cancer patients.Forty-six female patients (50 lesions) with histologically confirmed invasive breast cancer who underwent both F-FES and F-FDG PET/CT in our center were retrospectively included. All the patients enrolled were scheduled to undergo biopsy. The F-FES and FDG uptakes were compared with pathological features (tumor size, ER, progesterone receptor, human epidermal growth factor receptor 2, and Ki67%). The optimal threshold to discriminate ER-positive and ER-negative lesions was determined by receiver operating characteristic curve analysis. Furthermore, we observed the intratumoral heterogeneity by a heterogeneity index (SUVmax/SUVmean) and compared the results with the Chang-Gung Image Texture Analysis.There was good agreement between F-FES uptake and ER, progesterone receptor, and human epidermal growth factor receptor 2 expression (P0.001), and the use of SUVmean instead of SUVmax can provide a slightly better correlation. The optimal threshold for F-FES PET/CT to discriminate between ER-positive and ER-negative lesions, as determined by receiver operating characteristic curve analysis, was an SUVmax of 1.82 (sensitivity = 88.2% and specificity = 87.5%) and SUVmean of 1.21 (sensitivity = 85.3% and specificity = 93.7). Our simplified heterogeneity index-FES can easily observe ER heterogeneity. In addition, our results suggested that recurrent/metastatic patients and lesions located other than breast might have greater heterogeneity.F-FES PET/CT is a feasible, noninvasive method for assessing ER expression in breast cancer patients. Because intratumoral heterogeneity exists, F-FES PET/CT might better reflect the ER expression, especially in metastatic patients after treatment, thus assisting in making individualized treatment decisions.

Purpose To evaluate the value of fluorine-18 2-deoxy-2-d-glucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) in the detection of metastatic medullary thyroid cancer. Methods From November 2006 to November 2012, 50 medullary thyroid cancer patients (median age 48.7years, range 18–76) who had a total thyroidectomy operation underwent whole-body [ 18 F]FDG-PET/CT scans. The diagnostic accuracy of [ 18 F]FDG-PET/CT was determined through both lesion-based and patient-based analyses. Further pathological tests were performed on all identified lesions or clinically followed for a minimum period of 6months. Results One hundred forty-four suspicious lesions were identified by organ-based analysis. Of these lesions, [ 18 F]FDG-PET/CT detected 99 true-positive lesions, sensitivity was 73.3%, and specificity was 66.7%. On the patient-based analysis, the overall sensitivity and specificity were calculated as 65.7% and 92.3%, respectively. Using a cutoff calcitonin value of 1000pg/ml, in patients with calcitonin lower than this value, sensitivity and specificity were 42.9% and 91.0%, respectively. In patients with calcitonin exceeding this value, they raised to 77.3% ( χ 2 =4.392, P χ 2 =0.197, P >.05), respectively. Compared with conventional imaging modality, PET/CT scans detected more lesions in 10 patients (20.4%) and correctly changed the treatment in 8 patients (16.3%). Conclusion [ 18 F]FDG-PET/CT has excellent sensitivity and specificity, especially when the calcitonin value is higher than 1000pg/ml for detecting metastatic medullary thyroid cancer. Compared to conventional morphologic imaging methods, it provides additional information for diagnosis.

Aim Our study was to investigate the heterogeneity of estrogen receptor (ER) expression among tumor sites by using fluorine-18 ( 18 F) fluoroestradiol (FES) positron-emission tomography–computed tomography (PET-CT) imaging. Methods Thirty-two breast cancer patients underwent both 18 F-FES and 18 F fluorodeoxyglucose (FDG) PET-CTs from June 2010 to December 2011 in our center (mean age, 53 years; range, 27-77 years). We used the maximum standardized uptake value to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER + and ER − . The difference of heterogeneity between the initial patients and patients with recurrent or metastatic disease after treatments was assessed by using the χ 2 test. Also, the 18 F-FES uptake was compared with the 18 F-FDG uptake by use of Spearman correlation coefficients. Results A total number of 237 lesions in 32 patients were detected. Among them, most lesions (64.1% [152/237]) were bone metastasis. A striking 33.4-fold difference in 18 F-FES uptake was observed among different patients (maximum standardized uptake value range, 0.5 to approximately 16.7), and a 8.2-fold difference was observed among lesions within the same individual (1.0 to approximately 8.2). As for 18 F-FDG uptake, the difference was 11.6-fold (1.3 to approximately 15.1) and 9.9-fold (1.4 to approximately 13.8), respectively. In 28.1% (9/32) of the patients, both 18 F-FES + and 18 F-FES − metastases were present, which suggests partial discordant ER expression. After treatments, 37.5% (9/24) patients with recurrent or metastatic breast cancer showed heterogeneity, whereas no untreated patient was detected to exist discordant ER expression (χ 2 , 4.174; P 18 F-FES uptake showed a weak correlation with the 18 F-FDG uptake (ρ = 0.248; P Conclusion 18 F-FES and 18 F-FDG uptake varied greatly both within and among patients. 18 F-FES PET-CT demonstrated a conspicuous number of patients with the heterogeneity of ER expression.

The aim of this study was to evaluate the utility of 3'-deoxy-3'-F-fluorothymidine (F-FLT) PET/computed tomography (CT) imaging in the pretreatment evaluation of metastatic gastric cancer in comparison with F-fluorodeoxyglucose (F-FDG) PET/CT imaging.A total of 39 metastatic gastric cancer patients were enrolled in the study. Attenuation-corrected whole-body F-FLT and F-FDG PET/CT (low-dose CT) imaging was performed on two consecutive days before chemotherapy.Accumulation of focal activity was visible in primary tumors on F-FLT PET/CT in 36/39 patients and on F-FDG PET/CT in 37/39 patients, with sensitivities of 92.3 and 94.9%, respectively. Further, three of the 36 FLT-avid primary tumors were almost undetected because they were covered by a high background hepatic uptake. Because of the high physiological uptake of F-FLT in the liver [median maximum standardized uptake value (SUVmax) 5.5, range 4.5-8.3] and the bone marrow (median SUVmax 14.8, range 10.8-22.0), the sensitivity of F-FLT PET/CT versus F-FDG PET/CT for detecting liver metastases and bone metastases was 30.0% (6/20) versus 100% (20/20) and 1/5 (20.0%) versus 5/5 (100%), respectively (P0.05). Metabolically positive findings of lymph node, peritoneal, and ovarian metastases were similar between the two modalities: 96.8% (30/31) versus 93.5% (29/31), 89.5% (17/19) versus 94.7% (18/19), and 90.9% (10/11) versus 90.9% (10/11) of patients for F-FLT versus F-FDG, respectively (P0.05).F-FLT PET/CT imaging is not recommended for pretreatment assessment of metastatic gastric cancer as it is not competent enough to evaluate liver and bone metastases; moreover, the high background hepatic uptake may cover the gastric primary tumors located adjacent to the liver.

The aim of this study is to evaluate the volume differences between contrast-enhanced CT-based left ventricle (LV) and PET-CT-based LV and assess the impact of dose on the substructure volume differences in patients with left breast cancer treated with adjuvant radiotherapy. From October 2008 to February 2009, 14 patients with post-operatively confirmed left breast cancer were enrolled in the current study. The patients were scanned using contrast-enhanced CT for simulation, and 18F-FDG PET-CT was employed to display the structure of the left ventricle of each before radiotherapy (RT). The LV was delineated based on both contrast-enhanced CT and PET-CT. And other substructures, such as the left anterior descending coronary artery (LAD), were contoured in each patient, with the six-field simple intensity modulated radiotherapy (sIMRT) technique created for all. The mean volumes of the left ventricle based on contrast-enhanced CT (LV-CT) and PET-CT (LV-PET) were found to be 107.296 cm3 and 112.931 cm3, respectively ( p = 0.06). The volume of LV receiving ≥50% prescription dose was significantly correlated with the volume of the heart receiving the same dosage (γ = 0.869). There was less correlation between the volume of LAD and that of the heart under the same condition (γ = 0.22). As a conclusion, the left ventricle can be delineated effectively based on the image of PET-CT, the contrast-enhanced CT based LV can serve as an appropriate alternative. Moreover, the volume of LV receiving high dose in RT closely correlated with the volume of the heart using sIMRT technique, which may pave the way for further exploring radiation-induced cardiac injuries in patients with left breast cancer.

The purpose of the preliminary study was to investigate whether high specific activity (SA) of

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers.From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months.Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively.PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

OBJECTIVE To evaluate the use of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in the diagnosis of cutaneous extranodal natural killer/T-cell lymphoma, nasal type (C-ENK/T-NT). METHODS A total of 39 patients with newly diagnosed C-ENK/T-NT were enrolled between May 2006 and November 2013. Anatomic regions (n=429; five cutaneous and six extracutaneous regions per patient) were assessed using an F-FDG PET/CT scan and conventional staging methods (CSMs). F-FDG PET/CT and CSMs were compared and evaluated for their ability to detect tumor lesions and their influence on the staging and treatment strategies. Biopsy and clinical follow-up were used as the gold standard for diagnosis. RESULTS In total, 139 lesions were detected by CSMs and F-FDG PET/CT, of which there were 50 cutaneous and 89 extracutaneous-positive regions. F-FDG PET/CT detected 48 cutaneous and 88 extracutaneous regions. CSMs, however, detected only 34 cutaneous lesions and 61 extracutaneous lesions that were positive for malignancy (cutaneous comparison of PET/CT vs. CSMs, P

To analyze the mRNA and protein expression of CD80 and vascular endothelial growth factor (VEGF) in esophageal cancer (EC) tissue, investigate the causes of esophageal cancer cell escape from immune surveillance.We detected the CD80 and VEGF mRNA with reverse transcription polymerase chain reaction (RT-PCR), CD80 protein with flow cytometry, VEGF protein with immunohistochemistry in the cancer tissues in 118 EC patients, and the normal esophageal tissue as controls.The expression of CD80 mRNA and protein in cancer tissues were lower than that in the controls (p0.01, respectively), The CD80 protein expression in poor differentiation was lower than that in the well and moderate (P0.01), in the patients with lymph node metastasis lower than that with no metastasis (P=0.01), in stage IIIA patients lower than that in stages I and II patients (P=0.04); the VEGF mRNA and protein expression were just right opposite. The mean survival time in the CD80 positive group was significantly longer than that in the negative (p=0.041); while in VEGF positive group was lower than that in the negative (p=0.046). The CD80 expression of mRNA and protein were correlated negatively with VEGF in the cancer tissues (r=-0.82, -0.87, respectively).It is suggested that CD80 was impaired in the EC tissues and correlated with the clinicopathological characteristics and prognosis, which indicated the dysfunction of immune system and enhancing the progression of EC. The low expression of CD80 correlated with the overexpression of VEGF.

Multi functional probes possessing magnetic resonance imaging and single-photon emission computed tomography properties are favorable for the molecular imaging of cancers. In this study, ultra small super paramagnetic iron oxide nanoparticles, about 3.5 nm in size, were synthesized by the polyol method. The particles were functionalized using c(RGDyC) peptides and labeled with 99mTc to prepare molecular imaging probes for detecting tumor angiogenesis. The probes demonstrated good T1 (r1 = 8.2 s(-1) mM(-1)) and reasonable T2 contrast effects (r2 = 20.1 s(-1) mM(-1)) and could specifically target avβ3-positive cells, inducing more cell ingestion, unlike that in case of the control probes [functionalized with scrambled c(RADyC) peptides]. After the probes were injected into the mice bearing H1299 lung tumors, T1/T2-weighted magnetic resonance imaging and single-photon emission computed tomography revealed that they addressed tumor angiogenic vessels, which were distributed mainly in the peripheral region of tumors. Biodistribution studies indicated that tumor accumulation of the probes was significant [13.8 ± 9.6%ID/g (p0.01), which is more than that of the control probes, 4.5 ± 1.9%ID/g], and could be inhibited by free RGD peptides (6.0 ± 2.8%ID/g, p0.01). Our study demonstrated that the dual-contrast (T1/T2) magnetic resonance and dual-modal imaging probe based on ultra small superparamagnetic iron oxide nanoparticles is very promising for the molecular imaging of tumor angiogenesis.

The study compares the physical and biologically effective doses (BED) received by the heart and cardiac substructures using three-dimensional conformal RT (3D-CRT), intensity-modulated radiotherapy (IMRT), and simple IMRT (s-IMRT) in postoperative radiotherapy for patients with left-sided breast cancer. From October 2008 to February 2009, 14 patients with histologically confirmed left-sided breast cancer were enrolled and underwent contrast-enhanced computed tomography (CT) simulation and 18F-FDG positron emission tomography-CT to outline the left cardiac ventricle (LV) and other substructures. The linear-quadratic model was used to convert the physical doses received by critical points of inner heart to BED. The maximal dose, minimum dose, dose received by 99% of volume (D99) and dose received by 95% of volume (D95) in target areas were significantly better using IMRT and s-IMRT when compared with 3D-CRT (P

Objective To evaluate the clinical value of 16α-[18F]fluoroestradiol (18F-FES) PET/CT in assisting the individualized treatment decisions of breast cancer patients. Methods Thirty-three breast cancer patients, who underwent both 18F-FES and 18F-FDG PET/CT from July 2010 to March 2013 in our center, were enrolled in this preliminary study. All the patients used 18F-FES PET/CT as a diagnostic tool with a clinical dilemma. We used the maximum Standardized Uptake Value (SUVmax) to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER positive and negative lesions. All patients were clinically followed up at least 6 months. Results In evaluating equivocal lesions on conventional work-up group (n = 4), three lung lesions and another iliac lesion were enrolled. As for three lung lesions, 18F-FES PET/CT showed one lesion with high uptake, which suggested it was an ER positive metastasis. The other two lesions were 18F-FES negative, which meant an ER negative metastasis or secondary primary tumor. Additionally, one iliac lesion was detected by MRI. 18F-FDG uptake was high at the suspected lesion, whereas 18F-FES uptake was absent; In predicting origin of metastasis group (n = 2), two breast cancer patients had secondary primary tumors were collected. They were 18F-FES negative, which showed low possibility of metastasis from breast cancer and they were all confirmed by biopsy. In detecting ER status in metastasis group (n = 27), 18F-FES PET/CT showed increased 18F-FES uptake in all metastatic lesions in 11 patients; absent in all lesions in 13 patients; and the remaining 3 patients had both 18F-FES positive and negative lesions. Totally, on the basis of the 18F-FES PET/CT results, we found changes in the treatment plans in 16 patients (48.5%, 16/33). Conclusions 18F-FES PET/CT could assess the entire tumor volume receptor status; therefore, it may be used to assist the individualized treatment decisions of breast cancer patients.

Objective To find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma. Methods From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUV max were recorded as the sum of SUV max of primary tumor and cervical lymph nodes. Total SUV mean, Total MTV and Total TLG were calculated in the same way as Total SUV max. Results The median follow-up was 32 months (range, 23-68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUV max, SUV mean, MTV, and TLG of primary tumor, Total SUV max, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUV max was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUV max and SUV max-T, and between Total SUV max and SUV max-N(Spearman coefficient: 0.568 and 0.834; p = 0.000 and p = 0.000). Conclusions Preliminary results indicated that Total SUV max was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.

Bone metastasis occurs frequently in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to compare the clinical value of 18F-FDG PET/CT with that of 99mTc-MDP planar bone scintigraphy (PBS) for detecting bone metastasis in NPC patients.Thirty-five histologically proven NPC patients were enrolled in this retrospective study. They underwent both 18F-FDG PET/CT and PBS within 7 days in our department. In a lesion-based analysis, the skeletal system, excluding the head, was divided into four regions: the spine, the pelvis, the thorax, and the appendix. Bone metastasis was considered to be present by either biopsy or clinical follow-up for at least 6 months. PET/CT and PBS were compared by McNemar's paired-sample test.A total of 50 lesions were confirmed to be malignant (spine 27, thorax 11, pelvis 8 and appendix 4). Although PET/CT was found to be more sensitive on lesion level than PBS (sensitivity 70.0 versus 42.0%; P=0.044), there were still 14 metastatic (28.0%) lesions that could be detected by PBS while negative in PET/CT imaging. In a patient-based analysis, fifteen (42.9%) of 35 eligible patients were found to have bone metastasis. The sensitivity, specificity and accuracy of PET/CT was 60.0% (9/15), 100% (20/20) and 82.9% (29/35); as for PBS, it was 66.7% (10/15), 85.0% (17/20) and 77.1% (27/35), respectively. There was no statistical difference between PET/CT and PBS (P0.05).PBS, as a conventional imaging, should be used as an important complement for detecting bone metastasis in NPC patients.

OBJECTIVE:To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) (18)F-fluoroestradiol ((18)F-FES) and (18)F-fluorodeoxyglucose ((18)F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer. METHODS:Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both (18)F-FES and (18)F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion. RESULTS:Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002). CONCLUSIONS:Our study showed (18)F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers (18)F-FES and (18)F-FDG has complementary value should be further studied.

A 54-year-old metastatic breast cancer patient who had undergone chemotherapy and radiotherapy was transferred to our hospital for further treatment. We utilized (18)F-fluoroestradiol (FES) to assess the estrogen receptor (ER) status of metastatic lesions. Interestingly, high accumulation of (18)F-FES in pneumonia caused by radiation was detected. Hence, this draws oncologists' attention to the possible false-positive result of (18)F-FES, which may lead to inappropriate endocrine therapy.

Although endocrine therapy is an effective method to treat estrogen receptor (ER)-positive breast cancer, approximately 30%-40% of all hormone receptor-positive tumors display de novo resistance. The aim of our current study was to analyze whether (18)F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [(18)F-FMISO]) PET/CT could predict primary resistance to hormonal therapy in ER-positive breast cancer.Postmenopausal women who had ER-α-positive breast cancer, stages II-IV, and had never received prior endocrine therapy were prospectively enrolled in this study. Patients underwent both (18)F-FDG and (18)F-FMISO PET/CT scans before and after treatment. The hottest (18)F-FDG standardized uptake value (SUV) in the tumor foci, the SUVs at 2 and 4 h, and the TBR2 h and TBR4 h for the target lesions were calculated (TBR2 h = SUV2 hT/SUV2 hB and TBR4 h = SUV4 hT/SUV4 hB [TBR is the tumor-to-background ratio]). Clinical outcomes of primary endocrine therapy with letrozole were evaluated according to the criteria of the World Health Organization after at least 3 mo of treatment. Immunohistochemistry for markers of proliferation (Ki67) and hypoxia-induced factor 1α was performed on a subset of tumors that had undergone biopsy or surgery. Pearson and Spearman analysis was used to determine the correlation between the parameters of (18)F-FDG and (18)F-FMISO uptake and clinical or immunohistochemistry outcomes with a 0.01 threshold for statistical significance.A total of 45 lesions (13 primary, 32 metastatic) from 20 patients met the inclusion criteria in this study. Baseline (18)F-FDG and (18)F-FMISO PET/CT scans were obtained for 33 lesions from 16 patients. The correlation between baseline (18)F-FDG uptake and clinical outcome was weak and did not reach statistical significance (r = 0.37, P = 0.031). However, there was a significantly positive correlation between baseline (18)F-FMISO uptake (SUV2 hT, TBR2 h, SUV4 hT, and TBR4 h) and clinical outcomes after ≥3 mo of primary endocrine therapy with letrozole (r = 0.77, 0.76, 0.71, and 0.78, respectively; P0.0001). The application of a TBR4 h cutoff of ≥1.2 allowed the prediction of 88% of the cases of progressive disease (15/17). Despite poor correlation between (18)F-FMISO uptake and hypoxia-induced factor 1α expression, a marginal positive correlation between TBR4 h and Ki67 expression was measured (r = 0.51, P = 0.011) in a subset of malignant lesions acquired by biopsy or surgery.(18)F-FMISO PET/CT can be used to predict primary endocrine resistance in ER-positive breast cancer.

To investigate the prevalence and risk of thyroid incidentaloma identified by positron emission tomography/computed tomography (PET/CT).Historical cohort study.Fudan University Shanghai Cancer Center.A total of 15 948 non-thyroid disease patients who underwent fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT from November 2006 to September 2010 were included. They were divided into two groups: 12 080 patients for metastatic evaluation and 3868 patients for cancer screening. When thyroid incidentaloma was found, further diagnostic examination was conducted.Prevalence and risk of thyroid incidentaloma.The prevalence of incidental thyroid 18F-FDG uptake was approximately 2.5% (395 of 15 948). The prevalence of incidentaloma in healthy subjects (118 of 3868; 3.1%) was statistically higher than that in patients with suspected or known cancer (277 of 12 080; 2.3%) (p.05). Among 395 incidentalomas, 146 patients had further examinations (53 patients with histologic confirmations, 93 patients with clinical monitoring). Finally, 43 lesions were confirmed to be malignancies. Therefore, the cancer risk was 29.5% (43 of 146), and it was higher in cancer screening patients (24 of 59; 40.7%) than in alleged cancer patients (19 of 87; 21.8%) (p.05). As for FDG uptake pattern, the prevalence of thyroid cancer was 11.6% (5 of 43) and 36.9% (38 of 103) in the group of patients with diffuse and focal uptake, respectively (p.05). After logistic regression analysis, age, sex, maximal standardized uptake value, and calcification were the potent predictors of differentiation.The presence of focal uptake with high SUVmax and calcification detected on CT images correlates with a high likelihood of thyroid malignancy. When a focal thyroid incidentaloma is detected, further examination should be performed.

To investigate the value of whole-body fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for the detection of metastatic bladder cancer.From December 2006 to August 2010, 60 bladder cancer patients (median age 60.5 years old, range 32-96) underwent whole body positron emission tomography/computed tomography positron emission tomography/computed tomography. The diagnostic accuracy was assessed by performing both organ-based and patient-based analyses. Identified lesions were further studied by biopsy or clinically followed for at least 6 months.One hundred and thirty-four suspicious lesions were identified. Among them, 4 primary cancers (2 pancreatic cancers, 1 colonic and 1 nasopharyngeal cancer) were incidentally detected, and the patients could be treated on time. For the remaining 130 lesions, positron emission tomography/computed tomography detected 118 true positive lesions (sensitivity = 95.9%). On the patient-based analysis, the overall sensitivity and specificity resulted to be 87.1% and 89.7%, respectively. There was no difference of sensitivity and specificity in patients with or without adjuvant treatment in terms of detection of metastatic sites by positron emission tomography/computed tomography. Compared with conventional imaging modality, positron emission tomography/computed tomography correctly changed the management in 15 patients (25.0%).Positron emission tomography/computed tomography has excellent sensitivity and specificity in the detection of metastatic bladder cancer and it provides additional diagnostic information compared to standard imaging techniques.

The clinical significance of tumor-associated macrophages (TAMs) and CD3-zeta chain expression of tumor-infiltrating lymphocytes (TILs), and their correlation in human esophageal squamous cell carcinoma (SCC) are not very clear. Serial histological slides from 137 esophageal SCC patients who had undergone tumor resection were immunohistochemically studied with anti-CD68, anti-CD3-zeta and anti-CD3-epsilon antibodies. TAMs infiltration (expressed as macrophage index, M(phi)I) and CD3-zeta expression (judged by Z/E = CD3-zeta+ cells/CD3-epsilon+ cells ratio) in different tissue compartments were observed. We found that the total tumor tissue region had significantly higher macrophage density and lower CD3-zeta expression (mean +/- SD: M(phi)I(normal): 225.3 +/- 85.9; Z/E(total): 0.52 +/- 0.25; n = 137) relative to adjacent histologically normal esophageal squamous epithelium (M(phi)I(normal): 60.5 +/- 31.7, P < 0.001; Z/E(normal): 0.79 +/- 0.35, P = 0.001; n = 70). Significantly higher M(phi)I(stroma) (P = 0.006) and lower Z/E(total) (P = 0.016) were detected in patients with lymph node metastasis than in those without. Patients with high M(phi)I(total) and M(phi)I(cancer) but low Z/E(total) had poorer surgical outcomes. Univariate analysis of M(phi)I(total) and multivariate analysis of M(phi)I(total) with specific clinico-pathological parameters demonstrated M(phi)I(total) to be an independent prognostic factor for survival in esophageal SCC patients (Cox proportional hazard model, P = 0.029 and P = 0.031, respectively).

Objective: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe. Methods: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes. Results: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1–5 (mean 1.5) and non-sentinel nodes ranged from 5–22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours. Conclusions: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.

To evaluate the feasibility of lymphoscintigraphy in sentinel lymph node biopsy of breast cancer.Lymphoscintigraphy was performed after peritumoral or subdermal injection of radioactive colloid. Then, sentinel lymph node (SLN) biopsy guided by gamma detector probe was performed. Factors correlated with identification-detection rate were assessed.Lymphatic drainage was present in preoperative lymphoscintigraphy in 88(93%) out of 95 patients, with 39 (44.3%) positive for lymphatic drainage other than in the axilla. A total of 91 (95.8%) patients had their SLN identified in the intraoperative procedure. The quality of lymphoscintigraphic image was closely related to SLN identification-detection rate in the intraoperative procedure (P = 0.025).Sentinel lymph node outside the axilla can be detected by lymphoscintigraphy. The combination of lymphoscintigraphy and gamma detector probe for sentinel lymph node biopsy of breast cancer not only is acceptable but promising.