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Background/aim: To investigate the effect of positron emission tomography-computed tomography (PET/CT)-based contouring on dosimetric parameters in rectal cancer patients undergoing preoperative intensity-modulated radiation therapy (IMRT). Materials and methods: Preoperative radiation therapy plans with conformal radiotherapy (CRT) or IMRT were created and examined according to the CT- and PET/CT-based contouring of 20 rectal cancer patients, retrospectively. Results: The target volumes delineated with PET/CT were significantly larger than the volumes created by CT (P = 0.043). Dose delivered to 98% of the planning target volume was high in IMRT planning contouring with CT and PET/CT compared with CRT planning, but the difference was not statistically significant (P = 0.056). Percent volumes receiving 105% of dose and 110% of dose were low in IMRT planning when compared with CRT (P < 0.0001 and P = 0.044, respectively). The volumes receiving 45 Gy for the small intestine, femur heads, and bladder and the maximum dose received by the bladder were significantly lower in IMRT. Conclusion: We showed that the target volumes created with PET/CT are significantly larger than the target volumes created with CT and that IMRT provides lower radiation exposure to the tumor-free tissues compared to the CRT planning. The dosimetric results primarily favor IMRT planning in rectal cancer patients and consequently present the significant alteration in target volumes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to accurately differentiate between benign and malignant small renal masses (SRMs) prior to surgery. Methods: The study included 144 patients with SRMs <4 cm suspected to be renal cell carcinoma (RCC) based on several imaging examinations, who subsequently underwent partial nephrectomy. Clinicopathological data were analyzed based on the preoperative findings obtained from enhanced computed tomography (CT) as follows: group 1 showing a typical imaging pattern for clear cell RCC (CCRCC), and group 2 showing an imaging pattern atypical of CCRCC. We then evaluated the association between clinicopathological characteristics and pathological diagnosis in order to identify factors which can predict the pathological diagnosis. Results: Based on the criteria, 102 (70.8 %) and 42 (29.2 %) patients were classified into group 1 and group 2, respectively. The only independent factor identified to predict the final pathological diagnosis of the 144 patients was preoperative CT findings. Only 7 (6.9 %) patients were pathologically diagnosed with benign tumors in group 1; however, 13 (31.0 %) of the 42 patients in group 2 appeared to have pathologically confirmed benign tumors. A younger age and lower body mass index (BMI) in group 2 were shown to be independently associated with benign histology on multivariate analysis. Conclusions: The proportion of patients with benign tumors was comparatively high in those with CT findings atypical for CCRCC; therefore, other clinical parameters, such as age and BMI, should be considered when determining therapeutic strategies for patients with such SRMs. [ABSTRACT FROM AUTHOR]

Objectives: Karakiewicz et al. and Green et al. created pre-cystectomy nomograms to predict lymph node involvement. The aim of the study was to externally validate these two nomograms in intermediate-volume institutions in Europe. Patients and methods: Data from a Serbian single-centre cystectomy series comprising 183 patients with bladder cancer were used for the validation of two US nomograms, which were originally based on data from 726 and 201 patients, respectively. A multivariate regression model assessed the value of the clinical parameters integrated in the two nomograms. The expected predictive accuracy, calibration and clinical utility according to the nomograms were calculated. Results: Comparison of our dataset with the previously published data shows differences in nearly all underlying risk variables. Overall, 109 (59.6 %) patients had lymph node metastases. The analysis demonstrated that hydronephrosis and status of lymph nodes on computed tomography have independent prognostic value. The performance of the nomograms deteriorated from the development set, and the predictive accuracies for the two models showed moderate discriminatory ability (61.2-69.1 %). In the decision curve analysis, only the Green et al. model predicting lymph node positivity provided net benefit. Conclusions: The Green et al. nomogram seems applicable to patients from Europe, despite varying risk factors in the validation dataset. Acceptance of such a tool into daily clinical management may lead to more appropriate decision-making. Nevertheless, further improvement and implementation of novel statistical models with enhanced predictive accuracy is needed. [ABSTRACT FROM AUTHOR]

Molecular imaging is an attractive platform for noninvasive detection and assessment of cancer. In recent years, the targeted imaging of the C-X-C chemokine receptor 4 (CXCR4), a chemokine receptor that has been associated with tumor metastasis, has become an area of intensive research. This review article focuses on positron emission tomography (PET) and aims to provide useful and critical insights into the application of PET to characterize CXCR4 expression, including the chemical, radiosynthetic, and biological requirements for PET radiotracers. This discussion is informed by a summary of the different approaches taken so far and a comparison of their clinical translation. Finally, our expert opinions as to potential future advances in the field are expressed. [ABSTRACT FROM AUTHOR]

We aimed to quantitatively characterize the treatment effects of docetaxel in the HCT116 xenograftmouse model, applying diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) using 2-deoxy-2-[18 F]fluoro-D-glucose ([18F]FDG) and 3'-deoxy-3'-[18F]-fluorothymidine ([18F]FLT). Mice were imaged at four time points over 8 days. Docetaxel (15 mg/kg) was administered after a baseline scan. Voxel-wise scatterplots of PET and apparent diffusion coefficient (ADC) data of tumor volumes were evaluated with a threshold cluster analysis and compared to histology (GLUT1, GLUT3, Ki67, activated caspase 3a). Compared to the extensive tumor growth observed in the vehicle-treated group (from 0.32 ± 0.21 cm³ to 0.69 ± 0.40 cm³), the administration of docetaxel led to tumor growth stasis (from 0.32 ± 0.20 cm³ to 0.45 ± 0.23 cm³ ). The [18F]FDG/ADC cluster analysis and the evaluation of peak histogram values revealed a significant treatment effect matching histology as opposed to [18F]FLT/ADC. [18F]FLT uptake and the Ki67 index were not in good agreement. Our voxel-based cluster analysis uncovered treatment effects not seen in the separate inspection of PET and MRI data and may be used as an independent analysis tool. [18F]FLT/ADC cluster analysis could still point out the treatment effect; however, [18F]FDG/ADC reflected the histology findings in higher agreement. [ABSTRACT FROM AUTHOR]

Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro-computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhancedmicroCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) 5 .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring. [ABSTRACT FROM AUTHOR]

Background: The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the macroscopic classification of nodular hepatocellular carcinoma (HCC) as compared to angiography-assisted computed tomography (CT). Methods: A total of 71 surgically resected nodular HCCs with a maximum diameter of ≤5 cm were investigated. HCCs were evaluated preoperatively using Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT. HCCs were pathologically classified as simple nodular (SN), SN with extranodular growth (SN-EG), or confluent multinodular (CMN). SN-EG and CMN were grouped as non-SN. Five readers independently reviewed the images using a five-point scale. We examined the accuracy of both imaging modalities in differentiating between SN and non-SN HCC. Results: Overall, the area under the receiver operating characteristic curve ( A) for the diagnosis of non-SN did not differ between Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT [0.879 (95 % confidence interval (CI), 0.779-0.937) and 0.845 (95 % CI, 0.723-0.919), respectively]. For HCCs >2 cm, the A for Gd-EOB-DTPA-enhanced MRI was greater than 0.9. The sensitivity, specificity, and accuracy of Gd-EOB-DTPA-enhanced MRI for identifying non-SN were equal to or higher than values with angiography-assisted CT in all three categories (all tumors, ≤2 cm, and >2 cm), but the differences were not statistically significant. Conclusions: Using Gd-EOB-DTPA-enhanced MRI to assess the macroscopic findings in nodular HCC was equal or superior to using angiography-assisted CT. [ABSTRACT FROM AUTHOR]

The escalating costs of conventional diagnostic technology in oncology have yet to obviate futile surgery intervention and the spiralling treatment cost. The evolution in engineering technology which looks at the correlation of the anatomy and the function of tumours i.e. Positron Emission Tomography-Computed Tomography (PET-CT) have impacted on the improved diagnostic accuracy and treatment in oncology. Clinical data have demonstrated that the information provided by PET/CT often changes patient management. This review addresses the value of PET-CT as a surrogate molecular marker in rumours and to discuss some issues in adopting PET/CT in routine daily practice as supported by the numbers of literature reviews of its application in oncology since it was first commercialized in 2001. The description of the technology used in multimodality imaging has gained encouraging interest among physicians, policy makers and insurance companies on the importance of the PET-CT, for which roles are not limited to the staging, disease prognostication and treatment monitoring with potential impact on treatment cost and justification of radiation safety for the patient. PET/CT is a useful tool in cancer investigation as evidenced by its role as a surrogate marker in underpinning the cellular reprogramming of different pathological entities. [ABSTRACT FROM AUTHOR]

Homing is an inherent, complex, multistep process performed by cells such as human bone marrow mesenchymal stem cells (hMSCs) to travel from a distant location to inflamed or damaged tissue and tumors. This ability of hMSCs has been exploited as a tumor-targeting strategy in cell-based cancer therapy. The purpose of this study was to investigate the applicability of 111In-oxine for tracking hMSCs in vivo by combining single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). 111In-labeled hMSCs (106 cells) were infused intraperitoneally in neuroblastoma-bearing mice, whereas a control group received a dose of free 111In-oxine. SPECT and MRI studies were performed 24 and 48 hours afterwards. Initially, the images showed similar activity in the abdomen in both controls and hMSC-injected animals. In general, abdominal activity decreases at 48 hours. hMSC-injected animals showed increased uptake in the tumor area at 48 hours, whereas the control group showed a low level of activity at 24 hours, which decreased at 48 hours. In conclusion, tracking 111In-labeled hMSCs combining SPECT and MRI is feasible and may be transferable to clinical research. The multimodal combination is essential to ensure appropriate interpretation of the images. [ABSTRACT FROM AUTHOR]

Background/aim: Our purpose in this retrospective study was to determine the ratio of unexpected [metastases within the coverage area of thorax computed tomography (CT)] and unknown (metastases out of the coverage area of thorax CT) metastases by positron emission tomography/CT (PET/CT) in patients with newly diagnosed non-small cell lung cancer (NSCLC) who had no defined metastatic lesion, and to investigate the contribution of fludeoxyglucose (FDG)-PET/CT in metastasis staging. Materials and methods: A total of 567 patients (489 males and 78 females, mean age 60.9 ± 10.7 years) were enrolled in this study. Among the 567 patients, a total of 156 patients who underwent PET/CT for metabolic characterization (group 1) and had solitary pulmonary nodules (group 1a, n = 39) or solitary pulmonary masses (group 1b, n = 117) and the remaining 411 patients (group 2) with NSCLC who had PET/CT performed for staging formed the basis of this study. Results: In group 1, 5/39 (12.8%) patients with a solitary pulmonary nodule and 29/117 (24.8%) patients with a solitary pulmonary mass had distant metastases. In group 2, 129 patients of 411 (31.4%) had distant metastasis. Conclusion: FDG-PET/CT is proven to be an effective method in detection of unsuspected-unknown metastasis, either in patients with solitary pulmonary lesion or in the initial staging of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Chordomas are rare bone tumors, developed from the notochord and largely resistant to chemotherapy. A special feature of this tumor is the heterogeneity of its cells. By combining high pressure freezing (HPF) with electron tomography we were able to illustrate the connections within the cells, the cell-cell interface, and the mitochondria-associated endoplasmic reticulum membrane complex that appears to play a special role among the characteristics of chordoma. These lipid raft-like regions are responsible for lipid syntheses and for calcium signaling. Compared to other tumor cells, chordoma cells show a close connection of rough endoplasmic reticulum and mitochondria, which may influence the sphingolipid metabolism and calcium release. We quantified levels of ceramide and glycosylceramide species by the methyl tert-butyl ether extraction method and we assessed the intracellular calcium concentration with the ratiometric fluorescent dye Fura-2AM. Measurements of the changes in the intracellular calcium concentration revealed an increase in calcium due to the application of acetylcholine. With regard to lipid synthesis, glucosylceramide levels in the chordoma cell line were significantly higher than those in normal healthy cells. The accumulation of glycosylceramide in drug resistant cancer cells has been confirmed in many types of cancer and may also account for drug resistance in chordoma. This study aimed to provide a deep morphological description of chordoma cells, it demonstrated that HPF analysis is useful in elucidating detailed structural information. Furthermore we demonstrate how an accumulation of glycosylceramide in chordoma provides links to drug resistance and opens up the field for new research options. [ABSTRACT FROM AUTHOR]

Background: The clinical usefulness of positron emission tomography (PET) with F-fluorodeoxyglucose (FDG) for the detection of recurrent hepatocellular carcinoma (HCC) is controversial because HCC displays varying FDG avidity. The purposes of this study were to re-evaluate the utility of FDG PET for the detection of recurrent HCC, and to assess its prognostic value in a large series of postoperative patients. Methods: We retrospectively reviewed 113 scans in 86 patients undergoing FDG PET after curative surgery for HCC. These scans were performed for suspected recurrence on radiologic imaging (group A: n = 44) because of an elevated tumor marker level with negative prior imaging results (group B: n = 32) or with no suspicion of recurrence (group C: n = 37). FDG PET's accuracy for recurrence detection and its value as a predictor of survival were assessed. Results: The sensitivity, specificity, and diagnostic accuracy were 53, 100, and 55 % for group A; 34, 100, and 41 % for group B; and 11, 100, and 78 % for group C, respectively. A change in therapy resulted from the scan results in 7, 9, and 8 % in groups A, B, and C, respectively. The combined sensitivities for intra- and extrahepatic recurrence were 30 and 42 %, respectively. Histopathological features at initial surgery did not affect the sensitivity. The overall survival of patients with positive scans was significantly poorer than that of patients with negative scans ( P = 0.008). Conclusions: The sensitivity of FDG PET for recurrent HCC was low, with little change in treatment resulting. However, it can predict prognosis in postoperative patients. [ABSTRACT FROM AUTHOR]

Background: Whole-body cancer screening with multimodalities including [F]-fluorodeoxyglucose positron emission tomography (FDG-PET) detects a wide range of tumors. This program has been recognized as an option for opportunistic screening, particularly in Japan. However, reports on diagnostic accuracy have been limited. We aimed to evaluate the detectability and related properties of this screening program among asymptomatic individuals in a community setting. Methods: The study participants were 1,762 residents of Osaka Prefecture, Japan, who underwent opportunistic cancer screening at Higashitemma Clinic for the first time between November 2004 and December 2005. FDG-PET cancer screening was performed with several imaging modalities (e.g., FDG-PET, computed tomography, magnetic resonance imaging and ultrasonography) and fecal occult blood test. Screening records were linked to the Osaka cancer registry within 1 year after the screening to determine sensitivity, specificity and positive predictive values. Results: After excluding 12 participants with cancer detected before the screening, 33 were identified by the cancer registry to have primary cancers. Of these, the present screening program found that 28 were positive (6 prostate, 5 lung, 5 colorectal, 5 thyroid, 3 liver and 4 others). Sensitivity, specificity and positive predictive values were 84.8 % (28/33, 95 % confidence interval 69.1-93.3), 86.8 % (1,491/1,718, 85.1-88.3) and 10.1 % (28/277, 6.4-12.9), respectively. Conclusions: FDG-PET cancer screening with multimodalities reasonably and accurately detects existing asymptomatic cancer. However, the numbers of false negatives and false positives were not insignificant. Facilities that provide the screening should inform participants of relevant information, including the limitations of this program. [ABSTRACT FROM AUTHOR]

To investigate the relationships between tumor heterogeneity, assessed by texture analysis of [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) images, metabolic parameters, and pathologic staging in patients with non-small cell lung carcinoma (NSCLC). A retrospective analysis of 38 patients with histologically confirmed NSCLC who underwent staging FDG-PET/computed tomography was performed. Tumor images were segmented using a standardized uptake value (SUV) cutoff of 2.5. Five textural features, related to the heterogeneity of gray-level distribution, were computed (energy, entropy, contrast, homogeneity, and correlation). Additionally, metabolic parameters such as SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), as well as pathologic staging, histologic subtype, and tumor diameter, were obtained. Finally, a correlation analysis was carried out. Of 38 tumors, 63.2% were epidermoid and 36.8% were adenocarcinomas. The mean ± standard deviation values of MTV and TLG were 30.47 ± 25.17 mL and 197.81 ± 251.11 g, respectively. There was a positive relationship of all metabolic parameters (SUVmax, SUVmean, MTV, and TLG) with entropy, correlation, and homogeneity and a negative relationship with energy and contrast. The T component of the pathologic TNM staging (pT) was similarly correlated with these textural parameters. Textural features associated with tumor heterogeneity were shown to be related to global metabolic parameters and pathologic staging. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the accuracy, safety, and role of splenic biopsy in the management of patients with non-mass-forming isolated splenomegaly and suspected malignant lymphoma. Methods: Between 2001 and 2013, 137 biopsies were performed under computed tomography (CT) fluoroscopic guidance in 39 patients. All patients had splenomegaly based on the CT findings and a suspected diagnosis of malignant lymphoma based on their clinical symptoms. The spleen was the only accessible site to perform a biopsy, and no mass lesions could be identified in the spleen. Results: The overall sensitivity, specificity, and diagnostic accuracy of image-guided biopsy for malignant lymphoma were 88%, 100% and 92%, respectively. Major complications occurred in 3 patients. In 1 patient, transcatheter arterial embolization was performed due to hemorrhage, and two patients needed blood transfusion because of hematoma development, without the need for further treatment. Conclusions: Image-guided splenic core-needle biopsy is a safe and accurate technique with a high diagnostic accuracy in most patients who with non-mass-forming isolated splenomegaly and suspected underlying malignant lymphoma. [ABSTRACT FROM AUTHOR]

Yttrium-90 is known to have a low positron emission decay of 32 ppm that may allow for personalized dosimetry of liver cancer therapy with 90Y labeled microspheres. The aim of this work was to image and quantify 90Y so that accurate predictions of the absorbed dose can be made. The measurements were performed within the QUEST study (University of Sydney, and Sirtex Medical, Australia). A NEMA IEC body phantom containing 6 fillable spheres (10–37 mm ∅) was used to measure the 90Y distribution with a Biograph mCT PET/CT (Siemens, Erlangen, Germany) with time-of-flight (TOF) acquisition. A sphere to background ratio of 8∶1, with a total 90Y activity of 3 GBq was used. Measurements were performed for one week (0, 3, 5 and 7 d). he acquisition protocol consisted of 30 min-2 bed positions and 120 min-single bed position. mages were reconstructed with 3D ordered subset expectation maximization (OSEM) and point spread function (PSF) for iteration numbers of 1–12 with 21 (TOF) and 24 (non-TOF) subsets and CT based attenuation and scatter correction. Convergence of algorithms and activity recovery was assessed based on regions-of-interest (ROI) analysis of the background (100 voxels), spheres (4 voxels) and the central low density insert (25 voxels). For the largest sphere, the recovery coefficient (RC) values for the 30 min –2-bed position, 30 min-single bed and 120 min-single bed were 1.12±0.20, 1.14±0.13, 0.97±0.07 respectively. For the smaller diameter spheres, the PSF algorithm with TOF and single bed acquisition provided a comparatively better activity recovery. Quantification of Y-90 using Biograph mCT PET/CT is possible with a reasonable accuracy, the limitations being the size of the lesion and the activity concentration present. At this stage, based on our study, it seems advantageous to use different protocols depending on the size of the lesion. [ABSTRACT FROM AUTHOR]

Background: We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. Methods: We evaluated 176 patients with small lung adenocarcinomas (diameter, 1–3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography) with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion). Recurrence-free survival was used for prognosis. Results: Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0.60, 0.81, 0.81 and 0.65 for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Conclusions: According to the univariate analyses including a logistic regression and ROCs performed for variables with p-values of <0.05 on univariate analyses, our results suggest that measuring tumour size using mediastinal window on high-resolution computed tomography is a simple and useful preoperative prognosis modality in small adenocarcinoma. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor. [ABSTRACT FROM AUTHOR]

Purpose: Computed tomography (CT)-guided radiofrequency ablation (RFA) is safe and effective for patients with unresectable primary, recurrent, or metastatic thoracic malignancies. Several studies have shown the benefit of employing 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET) to follow thoracic malignancies treated with RFA. In this prospective study, we show the safety and therapeutic efficacy of RFA and the utility of FDG-PET as tool for early detection of local recurrence. Methods: Twenty patients were enrolled in this study, and 24 lesions were ablated. Seven lesions were primary lung cancer, and 17 lesions were recurrent tumors or metastases from extrathoracic sites. Tumor size was in the range of 0.4-3.3 cm in diameter (mean: 1.5 cm). CT and FDG-PET scans were scheduled 7-14 days and 3-6 months after RFA treatment. Results: There were 17 adverse events (70.8 %) in 24 ablations included 13 pneumothoraces, two cases of chest pain, and two episodes of fever. With a median follow-up of 35.9 months (range 1-62 months), the overall 2-year survival rate was 84.2 %. Local recurrence occurred at four sites (2-year local control rate was 74.3 %). The FDG-PET results 7-14 days after RFA did not predict recurrence, whereas positive findings 3-6 months after RFA significantly correlated with local recurrence ( p = 0.0016). Conclusions: We confirmed the effectiveness of RFA for unresectable primary and secondary thoracic malignancies. FDG-PET analysis 3-6 months after ablation is a useful tool to assess local control. [ABSTRACT FROM AUTHOR]

Lipoma is the most common benign mesenchymal neoplasm. About 16% of lipomas arise in the head and neck region, especially in the posterior neck. Large lipomas that originate from the retropharyngeal space may cause dyspnea, dysphagia, and snoring and occasionally may lead to obstructive sleep apnea syndrome (OSAS). Herein, we report a 45-year-old male patient with OSAS caused by a giant retropharyngeal lipoma with emphasis on CT findings. [ABSTRACT FROM AUTHOR]

Background: Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). Methods: All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. Results: Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). Conclusions: Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients. [ABSTRACT FROM AUTHOR]

Aim To assess the predictive value of fluorine-18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in early assessing response during neo-adjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. Materials and methods A systematic review was performed by search of MEDLINE Library for the following terms: “rectal carcinoma OR rectal cancer”, “predictive OR prediction OR response assessment OR response OR assessment”, “early OR ad interim ”, “therapy”, “FDG OR 18 F-FDG”, “PET OR PET/CT”. Articles performed by the use of stand-alone PET scanners were excluded. Results 10 studies met the inclusion criteria, including 302 patients. PET/CT demonstrated a good early predictive value in the global cohort (mean sensitivity = 79%; mean specificity = 78%). SUV and its percentage decrease (response index = RI) were calculated in all studies. A higher accuracy was demonstrated for RI (mean sensitivity = 82%; pooled specificity = 85%) with a mean cut-off of 42%. The mean time point to perform PET scan during CRT resulted to be at 1.85 weeks. Some PET parameters resulted to be both predictive and not statistical predictive of response, maybe due to the small population and few studies bias. Conclusion PET showed high accuracy in early prediction response during preoperative CRT, increased with the use of RI as parameter. In the era of tailored treatment, the precocious assessment of non-responder patients allows modification of the subsequent strategy especially the timing and the type of surgical approach. [ABSTRACT FROM AUTHOR]

Purpose This work sought to establish whether the choice of CT scanner calibration curve has a significant effect on dose computation using density correction methods for chest cancer. Material and methods CIRS ® 062 phantom was used to calculate the Hounsfield Unit using 80, 120 and 140 kV. Four CT calibration curves were implanted in the Eclipse ® TPS. Forty-two irradiation fields for 4 patients with lung cancer were included and analysed. The patients were treated with 3-dimensional radiation therapy. For each patient, 3 treatment plans were generated using exactly the same beam configuration. In plan 1, the dose was calculated using the Modified Batho (MB) method. In plan 2, the dose was calculated using the Batho power law (BPL) method. In plan 3, the dose was calculated using the Equivalent Tissue Air Ratio (ETAR) method. To evaluate the treatment plans computed by the three methods, the monitor units, dose volume histograms, conformity index, homogeneity index, planning target volumes conformity index, geometrical index and 2D gamma index were compared. The statistical analysis was carried out using Wilcoxon signed rank test. Results The three density correction methods in plans 1, 2 and 3 using tested curves produced a difference less than 1% for MUs and DVH. Wilcoxon test showed a statically significant difference for MUs using ETAR method with calibration curves based on 80 and 120 kV. There was no significant difference for the quality indices between plan 1, 2 and 3, ( P > 0.05), but a significant difference for the planning target volumes conformity index between plans 1, 2 and 3 ( P < 0.05) was observed. The 2D gamma analysis showed that 100% of pixels had gamma ≤ 1. Conclusion The impact of the modification of CT calibration curves on dose is negligible for chest cancer using density correction methods. One calibration curve can be used to take into account the density correction for lung. [ABSTRACT FROM AUTHOR]

Purpose: To determine the frequency and appearance of radiation-induced liver disease on PET/CT in patients undergoing serial imaging during neoadjuvant chemoradiation of distal esophageal cancer. Materials and methods: In this IRB-approved, HIPAA-compliant retrospective analysis, we identified 112 patients with distal esophageal cancer treated by neoadjuvant chemoradiation who had serial PET/CT imaging available for review. Two readers reviewed all studies in consensus and recorded those cases where new foci of visually detectable increased FDG avidity appeared in the liver during therapy. The etiology of such foci was determined from corresponding findings at CT or MRI, by hepatic biopsy during surgery, by characteristic evolution on post-operative imaging, or by a combination of these methods. Results: New foci of FDG avidity developed in the liver during neoadjuvant therapy in 10 of 112 (9%) patients, of whom nine (8%) were determined to have radiation-induced liver disease based on further imaging and/or biopsy and one of whom had developed interval metastatic disease based on biopsy. In the cases of radiation-induced liver disease, the abnormal foci were found only in the caudate and left hepatic lobes, near the primary tumor, while the patient who developed interval metastatic disease had involvement of the inferior right hepatic lobe, remote from the radiation therapy field. Conclusion: New foci of increased FDG avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation of distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease. [ABSTRACT FROM AUTHOR]

Purpose: To assess the accuracy of water-enema multidetector computed tomography (WE-MDCT) in extra-rectal colon cancer staging. Materials and methods: Fifty-three patients (mean age 70 years) with extra-rectal colon cancer proven by colonoscopy and biopsy were prospectively evaluated by preoperative WE-MDCT. CT scans were both intraluminal (water enema or WE) and intravenous (iodinated) contrast enhanced (CE). All patients underwent surgery. Tumors were classified with the TNM staging system. Noted CT features were: tumor size and location; tumor form and edges; spread to the pericolic fat or neighboring organs; thickening of retroperitoneal fascia; number, size, and enhancement of the peritumoral lymph nodes. Tumors were classified on CT into 3 T-stage groups: T1/T2, T3, and T4. Lymph nodes were classified by their density after injection [positive over 100 Hounsfield units (HU)]. Results: Tumor localization to the specific colon segment was correct in all the cases. The agreement between WE-MDCT staging and histopathology staging was good ( k = 0.64). An irregular and bowl-shaped aspect of the external edges of tumor provided excellent sensitivity for T3/T4 inclusion (Se 97.7%, NPV 85.7%). Thickening of a fascia or the abdominal wall provided good specificity for T4 stage (Sp 88.1%, NPV 94.9%). Enhancement over 100 HU of at least one peritumoral lymph node was the best criterion of N+ staging (Sp 67.7%, NPV 87.5%). Conclusion: WE-MDCT permits good staging of colon cancer based on objective features. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether asymmetric spermatic cord vessel enhancement (ASE) on contrast-enhanced computed tomography (CECT) indicates scrotal pathology. Methods: Sixty-one male patients with scrotal symptoms who underwent both scrotal ultrasound (US) and CECT within 24 h were identified through a radiology information system. Twenty-eight emergency department patients who underwent CECT only for unrelated symptoms were included for comparison. Two blinded radiologists independently reviewed each CECT scan for qualitative ASE. These data were compared with US diagnoses, when present. A third blinded radiologist reviewed each CECT scan for quantitative ASE by measuring Hounsfield unit (HU) density ratios. McNemar, Kappa, Student's t test, and ANOVA were used for analysis. Results: Eighty-nine total patients included 28 with CECT only and 61 with CECT and US, of which 41 had abnormal US: 15 acute epididymitis and/or orchitis, 7 testicular neoplasms, 11 varicoceles, and 8 with other pathologies. Twenty patients with normal US and 28 patients with CECT only served as control groups. Identification of ASE agreed with US diagnosis of epididymitis (and/or orchitis) or testicular neoplasm (reader 1: κ = 0.79, reader 2: κ = 0.75) with average 95.5% sensitivity and 88.8% specificity, and no significant difference between readers ( p = 0.58). For epididymitis (and/or orchitis) or testicular neoplasm patients, the average ratio of spermatic cord HU density (ipsilateral:contralateral) was significantly different from other patients (4.01 vs. 1.26, p = 0.0025). Conclusion: ASE on CECT shows stronger correlation with epididymitis (and/or orchitis) and testicular neoplasm compared with other scrotal pathologies. If discovered on CECT, this should prompt further clinical and/or imaging workup. [ABSTRACT FROM AUTHOR]

Lobular capillary hemangiomas (LCH) are acquired benign vascular tumors of skin and mucosal spaces of head and neck. Very few cases of LCH have been reported in the abdomen, predominantly occurring as mucosal polyps in the bowel. We present CT imaging features of solitary retroperitoneal LCH in a patient with synchronous ipsilateral renal cell carcinoma and review the available literature and imaging features in abdominal and extra-abdominal LCH. To our knowledge, there is no other case of retroperitoneal LCH available in the English literature. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. The major goal of imaging techniques is to correctly differentiate between benign and malignant renal lesions. We present the cases of six patients with renal masses that were interpreted completely differently based on ultrasound (US) and computerized tomography (CT) findings. From January 1st, 2008 to March 1st, 2014, 307 patients from our center underwent nephrectomy for RCC. In all patients US and CT were performed before the operation. In six patients, the US indicated a focal, solid renal lesion that was interpreted by CT as a cystic lesion (Bosniak II-III). Because discrepancies were evident, renal biopsies were performed. The biopsies revealed RCC in the six patients, all of whom underwent subsequent nephrectomy. All of the patients were confirmed to have macroscopically solid RCC without any cystic components. In most cases, CT is the most accurate diagnostic technique for the clinical diagnostic classification of renal masses. In cases where US characterizes a renal lesion as solid, despite CT findings of a cystic lesion, kidney biopsies are recommended. The 6 cases reported here support our belief that, in diagnostic processes of RCC, these techniques should be complementary used. [ABSTRACT FROM AUTHOR]

Objectives: To examine the value of CEUS as a non-invasive tool in detecting lateral neck metastasis (LNM) and the enhancement patterns of malignant lymph nodes (LN) for thyroid cancer patients. Methods: Eighty-two consecutive patients, who underwent both preoperative non-enhanced US and CEUS examinations, were retrospectively reviewed. All patients underwent lateral neck dissection (LND). Enhancement patterns of 102 collected LNs matching to CEUS findings were analyzed. Results: CEUS detected LNM in 53 of 65 patients, showing a higher sensitivity and accuracy than that of conventional US ( p = 0.109 and p = 0.154, respectively). Thirteen patients' surgical procedures were altered by CEUS findings, including nine true positive and four false positive cases. Five patients' surgical procedures were altered by conventional US findings, including two true positive and three false positive cases. Heterogeneous enhancement, perfusion defects, microcalcification, and centripetal/hybrid enhancement were all specific criteria for malignant LNs in univariate analysis. In multivariate analysis, only heterogeneous enhancement and centripetal/hybrid enhancement were significantly related to LN metastasis ( p = 0.000 and p = 0.037, respectively). Conclusions: CEUS may be a potential tool to facilitate conventional US in detecting LNM. Heterogeneous enhancement and centripetal/hybrid enhancement are useful criteria to distinguish between malignant and benign LNs. Key Points: • CEUS findings facilitated conventional US in detecting LNM. • Heterogeneous, centripetal/hybrid enhancement, microcalcification and perfusion defects were specific criteria of malignant LNs. • Heterogeneous and centripetal/hybrid enhancement were significantly related to LN metastasis in multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer deaths. Radiation therapy (RT), alone or in combination with chemotherapy, is the standard of care for curative intent treatment of patients with locally advanced or inoperable NSCLC. The ability to intensify treatment to achieve a better chance for cure is limited by the risk of injury to the surrounding lung. Methods/Design: This is a prospective observational study of 60 patients with NSCLC receiving curative intent RT. Independent human ethics board approval was received from the Peter MacCallum Cancer Centre ethics committee. In this research, Galligas and Gallium-68 macroaggregated albumin (MAA) positron emission tomography (PET) imaging will be used to measure ventilation (V) and perfusion (Q) in the lungs. This is combined with computed tomography (CT) and both performed with a four dimensional (4D) technique that tracks respiratory motion. This state-of-the-art scan has superior resolution, accuracy and quantitative ability than previous techniques. The primary objective of this research is to observe changes in ventilation and perfusion secondary to RT as measured by 4D V/Q PET/CT. Additionally, we plan to model personalised RT plans based on an individual's lung capacity. Increasing radiation delivery through areas of poorly functioning lung may enable delivery of larger, more effective doses to tumours without increasing toxicity. By performing a second 4D V/Q PET/CT scan during treatment, we plan to simulate biologically adapted RT depending on the individual's accumulated radiation injury. Tertiary aims of the study are assess the prognostic significance of a novel combination of clinical, imaging and serum biomarkers in predicting for the risk of lung toxicity. These biomarkers include spirometry, 18 F-Fluorodeoxyglucose PET/CT, gamma-H2AX signals in hair and lymphocytes, as well as assessment of blood cytokines. Discussion: By correlating these biomarkers to toxicity outcomes, we aim to identify those patients early who will not tolerate RT intensification during treatment. This research is an essential step leading towards the design of future biologically adapted radiotherapy strategies to mitigate the risk of lung injury during dose escalation for patients with locally advanced lung cancer. [ABSTRACT FROM AUTHOR]

Background: Axillary lymph node (ALN) status is an important prognostic factor for breast cancer. We retrospectively used contrast-enhanced computed tomography (CE-CT) to evaluate the presence of ALN, metastasis based on size, shape, and contrasting effects. Methods: Of 131 consecutive patients who underwent CE-CT followed by surgery for breast cancer between 2005 and 2012 in our institution, 49 were histologically diagnosed with lymph node metastasis. Maximum Hounsfield units (HU) and mean HU were measured in non-contrasting CT (NC-CT) and CE-CT of ALNs. Results: Of 12 examined measurements, we found significant differences between negative and metastatic ALNs in mean and maximum NC-CT HU, and mean and maximum CE-CT HU (P < 0.05). We used a receiver operating curve, to determine cut-off values of four items in which significant differences were observed. The highest accuracy rate was noted for the cut-off value of 54 as maximum NC-CT HU for which sensitivity, specificity, and accuracy rate were 79.6%, 80.5% and 80.2%, respectively. Conclusions: CT HU of a patient with breast cancer are absolute values that offer objective disease management data that are not influenced by the screener's ability. [ABSTRACT FROM AUTHOR]

The growth of solid tumours necessitates angiogenesis. The aim of this paper is the presentation and evaluation of different ex vivo methods for analysing tumour angiogenesis. Oral squamous cell carcinomas (SCC) were induced in mice by subcutaneous injection of tumour cells in the groin region and processed for histology and microvascular corrosion casting. Vascularization was analysed light microscopically using CD31 immunochemistry. Corrosion casts were analysed by scanning electron microscopy (SEM), micro computed tomography (μCT) and synchrotron radiation-based micro computed tomography (SRμCT). Immunochemistry allows for a simple and authentic detection and stereological quantification of the SCC vascularization. μCT imaging of the corrosion casts gives a high-quality overview over the three-dimensional (3D) microvascular architecture. SEM and SRμCT allow a high-definition display of the vessel morphology, providing magnificent detail recognition down to the capillary level enabling imaging of different forms of tumour angiogenesis, e.g., sprouting and intussusceptive angiogenesis. Immunochemistry and SEM are regarded as suitable for most of the morphometrical and morphological assessments because of the simple procedure and the high explanatory power, especially in combination with each other. High resolution SRμCT helps answering specialized questions, however, requires sophisticated data processing for visualization and is of limited availability. [ABSTRACT FROM AUTHOR]

Objectives: Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans. Methods: A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past history of cancer and metabolic bone diseases including but not limited to osteoporosis, osteopenia and Paget’s disease. Eleven studies met all the criteria. Results: The average normal SUVmax values from 11 patients were: cervical vertebrae 6.84 (range 4.38–8.64), thoracic vertebrae 7.36 (range 6.99–7.66), lumbar vertebrae 7.27 (range 7.04–7.72), femoral head 2.22 (range 1.1–4.3), humeral head 1.82 (range 1.2–2.9), mid sternum 5.51 (range 2.6–8.1), parietal bone 1.71 (range 1.3–2.4). Conclusion: According to our study, various skeletal sites have different normal SUV values. SUV values can be different between the normal bones and bones with tumor or metabolic bone disease. SUV can be used to quantify NaF-18 PET/CT studies. If the SUV values of the normal skeleton are known, they can be used in the characterization of bone lesions and in the assessment of treatment response to bone diseases. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer is one of the most common forms of cancer, and the development of novel tools for detection and efficient treatment of metastases is needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (PET) imaging and radioimmunotherapy. Since carcinoembryonic antigen (CEA) is an important target in colorectal cancer, the CEA-specific M5A antibody has been extensively studied in subcutaneous xenograft models; however, the M5A antibody has not yet been tested in advanced models of liver metastases. The aim of this study was to investigate the 64Cu-DOTA-labeled M5A antibody using PET in mice bearing CEA-positive liver metastases. Procedures: Mice were injected intrasplenically with CEA-positive C15A.3 or CEA-negative MC38 cells and underwent micro-computed tomography (micro-CT) to monitor the development of liver metastases. After metastases were detected, PET/MRI scans were performed with 64Cu-DOTA-labeled M5A antibodies. H&E staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET/MRI findings. Results: PET/MRI showed that M5A uptake was highest in CEA-positive metastases. The %ID/cm3 (16.5%±6.3%) was significantly increased compared to healthy liver tissue (8.6%±0.9%) and to CEA-negative metastases (5.5%±0.6%). The tumor-to-liver ratio of C15A.3 metastases and healthy liver tissue was 1.9±0.7. Autoradiography and immunostaining confirmed the micro-CT and PET/MRI findings. Conclusion: We show here that the 64Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy. [ABSTRACT FROM AUTHOR]

Aims Having incorporated PET-CT as part of the staging process for colorectal liver metastases (CRLM) in our unit since 2008, this study aims to evaluate the survival outcomes of all patients managed by our specialist multi-disciplinary team (MDT). Methods All patients with colorectal liver metastases referred to a single liver MDT between 2008 and 2011 were examined. Overall survival (OS) for palliative groups due to occult extrahepatic disease detected by PET-CT (A) and those upfront palliative patients with extensive multi-site disease as identified on baseline CT or disease progression during chemotherapy (B), and resected (C) groups were evaluated and compared. Different extents of occult extrahepatic disease as characterised by PET-CT were also compared. Results 532 patients were included in the study. Median OS for group A (n = 80), B (n = 161) and C (n = 291) were 10.9, 12.0 and 46.7 months, with a 5-year OS approaching 6.5%, 6.1% and 43.0% respectively. There were significant differences in OS of C vs. A & B (p < 0.001). Single compartment metastases had a significant better survival outcomes than non-torso metastases (p = 0.04). Conclusion This is the first report of OS of patients with CRLM excluded from surgery on the basis of PET-CT. We have confirmed that PET-CT is effective in selecting patients with occult extrahepatic disease, which has poor survival outcomes. However, a subgroup with single compartment extrahepatic disease has a better than expected outcome. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is an imaging technology that can detect and characterize tumors based on their molecular and biochemical properties, such as altered glucose, nucleoside, or amino acid metabolism. PET plays a significant role in the diagnosis, prognostication, and treatment of various cancers, including brain tumors. In this article, we compare uptake mechanisms and the clinical performance of the amino acid PET radiotracers (L-[methyl-11C]methionine [MET], 18F-fluoroethyl-tyrosine [FET], 18F-fluoro-L-dihydroxy-phenylalanine [FDOPA], and 11C-alpha-methyl-L-tryptophan [AMT]) most commonly used for brain tumor imaging. First, we discuss and compare the mechanisms of tumoral transport and accumulation, the basis of differential performance of these radioligands in clinical studies. Then we summarize studies that provided direct comparisons among these amino acid tracers and to clinically used 2-deoxy-2[18F]fluoro-D-glucose [FDG] PET imaging. We also discuss how tracer kinetic analysis can enhance the clinical information obtained from amino acid PET images. We discuss both similarities and differences in potential clinical value for each radioligand. This comparative review can guide which radiotracer to favor in future clinical trials aimed at defining the role of these molecular imaging modalities in the clinical management of brain tumor patients. [ABSTRACT FROM AUTHOR]

Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9∶1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP-HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1±4.8% and 97.6±16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3–21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST-pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. Methods: We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5th–97.5th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets. Results: Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780. Conclusion: Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. [ABSTRACT FROM AUTHOR]

Introduction: The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer. Methods: Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR). Results: At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29–11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE. Conclusion: Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoradiotherapy ( CRT) before surgery results in a pathological complete response ( pCR) rate in about 1/3 of the patients, which is correlated with survival. It was hypothesized that volumetric tumor response to CRT would correlate with outcomes. Patients who completed trimodality therapy, where planning, pre-, and post- CRT computed tomography scans were available, and pathology was reviewed by a central pathologist, were eligible for analysis. Absolute and relative tumor volume change pretreatment and post-treatment were correlated with pCR, locoregional recurrence ( LRR), disease-free survival, and overall survival. Fifty-six patients were analyzed. pCR was observed in 30% of patients. Median follow up was 20.3 (range 4-89) months. The 2- and 4-year overall survival was 61.3% (95% confidence interval [ CI]: 45-74) and 25.0% (95% CI: 11-41); proportion disease free was 32.1% (95% CI: 19-46) and 20.6% (9-36) at 2 and 4 years, respectively. The median relative volume reduction was 17% (95% CI: −24, −3%). Using 20% as the criteria, the proportion of patients with pCR of ≥20% versus <20% was 13/25 (52%) versus 4/31 (13%) for those who did not (odds ratio 7.3; 95% CI: 2-27). The LRR at 2 and 4 years were 29.5% (95% CI: 16-43) and 36.2% (95% CI: 23-50). The relative tumor reduction ≥20% was significantly correlated with LRR (hazard ratio 0.24; 95% CI: 0.07-0.8; p 0.02) at 2 and 4 years, respectively. Relative tumor volume reduction following CRT is correlated with pCR and LRR. Further investigations are warranted to examine the effect of volume change, alone or in conjunction with other factors as potential predictors for pathological response. [ABSTRACT FROM AUTHOR]

Purpose: Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. Materials and Methods: We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. Results: A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). Conclusions: The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. [Copyright &y& Elsevier]

Angiogenesis in breast cancer helps fulfill the metabolic demands of the progressing tumor and plays a critical role in tumor metastasis. Therefore, various imaging modalities have been used to characterize tumor angiogenesis. While micro-CT (μCT) is a powerful tool for analyzing the tumor microvascular architecture at micron-scale resolution, magnetic resonance imaging (MRI) with its sub-millimeter resolution is useful for obtaining in vivo vascular data (e.g. tumor blood volume and vessel size index). However, integration of these microscopic and macroscopic angiogenesis data across spatial resolutions remains challenging. Here we demonstrate the feasibility of 'multiscale' angiogenesis imaging in a human breast cancer model, wherein we bridge the resolution gap between ex vivo μCT and in vivo MRI using intermediate resolution ex vivo MR microscopy (μMRI). To achieve this integration, we developed suitable vessel segmentation techniques for the ex vivo imaging data and co-registered the vascular data from all three imaging modalities. We showcase two applications of this multiscale, multi-modality imaging approach: (1) creation of co-registered maps of vascular volume from three independent imaging modalities, and (2) visualization of differences in tumor vasculature between viable and necrotic tumor regions by integrating μCT vascular data with tumor cellularity data obtained using diffusion-weighted MRI. Collectively, these results demonstrate the utility of 'mesoscopic' resolution μMRI for integrating macroscopic in vivo MRI data and microscopic μCT data. Although focused on the breast tumor xenograft vasculature, our imaging platform could be extended to include additional data types for a detailed characterization of the tumor microenvironment and computational systems biology applications. [ABSTRACT FROM AUTHOR]

Automated whole breast ultrasound (ABUS) is becoming a popular screening modality for whole breast examination. Compared to conventional handheld ultrasound, ABUS achieves operator-independent and is feasible for mass screening. However, reviewing hundreds of slices in an ABUS image volume is time-consuming. A computer-aided detection (CADe) system based on watershed transform was proposed in this study to accelerate the reviewing. The watershed transform was applied to gather similar tissues around local minima to be homogeneous regions. The likelihoods of being tumors of the regions were estimated using the quantitative morphology, intensity, and texture features in the 2-D/3-D false positive reduction (FPR). The collected database comprised 68 benign and 65 malignant tumors. As a result, the proposed system achieved sensitivities of 100% (133/133), 90% (121/133), and 80% (107/133) with FPs/pass of 9.44, 5.42, and 3.33, respectively. The figure of merit of the combination of three feature sets is 0.46 which is significantly better than that of other feature sets (p \mathchar"702D value< 0.05). In summary, the proposed CADe system based on the multi-dimensional FPR using the integrated feature set is promising in detecting tumors in ABUS images. [ABSTRACT FROM AUTHOR]

Emerging idea in asthma phenotyping, incorporating local morphometric information on the airway wall thickness would be able to better account for the process of airway remodeling as indicator of pathology or therapeutic impact. It is thus important that such information be provided uniformly along the airway tree, not on a sparse (cross-section) sampling basis. The volumetric segmentation of the airway wall from CT data is the issue addressed in this paper by exploiting a patient-specific surface active model. An original aspect taken into account in the proposed deformable model is the management of auto-collisions for this complex morphology. The analysis of several solutions ended up with the design of a motion vector field specific to the patient geometry to guide the deformation. The segmentation result, presented as two embedded inner/outer surfaces of the wall, allows the quantification of the tissue thickness based on a locally-defined measure sensitive to even small surface irregularities. The method is validated with respect to several ground truth simulations of pulmonary CT data with different airway geometries and acquisition protocols showing accuracy within the CT resolution range. Results from an ongoing clinical study on moderate and severe asthma are presented and discussed. [ABSTRACT FROM AUTHOR]

Background: Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT) based texture analysis (QTA) has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC) and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC. Methods: Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival. Results: QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI) of 96.3% (78.1–100), 81.0% (50.5–97.4), and 89.6% (72.9–97.0); respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival. Conclusions: Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: CT has been found superior to chest x-ray to detect lung malignances. However, indeterminate lung lesions (ILL) are found in 4–42% by using CT in staging colorectal cancer (CRC) patients. Our aim was to examine the frequency of ILL on staging CT and the rate of the ILL being malignant, and to investigate if PET/CT was useful in pointing out the malignant cases. Methods: A prospective analysis of 238 consecutive patients operated for CRC followed median 24 months. All the patients had a preoperative staging CT. Patients with ILL had a PET/CT scan performed 3 months postoperatively and low dose chest CT performed 6, 12, 18 and 24 months postoperatively. Results: Twenty percent of the patients had ILL. Four of these patients (8.5%) had lung metastases detected median 9 months postoperatively, while 2 (4.3%) had other lung malignancies. One patient had TB. In patients with normal staging chest CT 10 of the 185 patients (5.4%) developed lung metastases detected median 16 months postoperatively. This was significantly later than in patients with ILL (p < 0.001), but with regard to the number of patients developing lung metastases no significant difference was found between the groups (p = 0.12). Conclusions: Even though a relative low number of ILL turn out to be malignant it seems advisable to use PET/CT scan in the follow-up to detect lung metastases as early as possible to better the prognosis. For the same reason all CRC patients should have chest CT included in their follow-up 6–12 months postoperatively. [Copyright &y& Elsevier]

Purpose: To analyze the technical success and tumor response of ultraselective transcatheter arterial chemoembolization (TACE) for small hepatocellular carcinoma (HCC) using automated tumor-feeders detection (AFD) software. Methods: Prototype AFD software was prospectively applied to cone-beam computed tomography images acquired during TACE for 155 consecutive HCCs ≤50 mm in 81 patients. The detectability of tumor-feeding subsubsegmental arteries was analyzed. Technical success of TACE was classified into three grades according to 1-week CT; the tumor was embolized with a safety margin (5 mm wide for tumors <25 mm, and 10 mm wide for tumors ≥25 mm) (grade A), without a margin in parts (grade B), or the entire tumor was not embolized (grade C). Tumor response at 2-3 months after TACE was also evaluated in 71 patients using the modified Response Evaluation Criteria in Solid Tumors. Results: One-hundred and twenty-eight (82.6%) tumors were classed as grade A, 17 (11%) as grade B, and 10 (6.5%) as grade C. AFD software could identify 211 (85.4%) of 247 tumor-feeders but not 36 (14.6%). Eighteen (7.9%) were false positive. The tumor response of target lesions in each patient was complete response (CR) in 49 (69%) patients, partial response (PR) in 19 (26.8%), and stable disease (SD) in 3 (4.2%). The overall tumor response was CR in 39 (54.9%) patients, PR in 15 (21.2%), SD in 1 (1.4%), and progressive disease in 16 (22.5%). Conclusions: AFD software has sufficient performance to identify tumor-feeders and contributes to the high technical success in ultraselective TACE. [ABSTRACT FROM AUTHOR]