Evaluation of the Metabolic Response to Cyclopamine Therapy in Pancreatic Cancer Xenografts Using a Clinical PET-CT System

OBJECTIVES: We analyzed the effects of anti-hedgehog signaling on the ¹⁸F-FDG uptake of pancreatic cancer xenografts (PCXs) using a clinically implemented positron emission tomography (PET)-computer tomography (CT) scanner with high-resolution reconstruction. METHODS: PCXs from two pancreatic cancer cell lines were developed subcutaneously in nude mice and injected intraperitoneally with a low dose of cyclopamine for 1 week. ¹⁸F-FDG PET-CT was performed using a new-generation clinical PET-CT scanner with minor modifications of the scanning protocol to adapt for small-animal imaging. The data set was reconstructed and quantified using a three-dimensional workstation. RESULTS: MiaPaCa-2 cells, which respond to cyclopamine, showed decreased ¹⁸F-FDG uptake without a change in tumor size. For hip tumors, the maximum standardized uptake value (SUV_max) was reduced by -24.5 ± 9.2%, the average SUV (SUV_avg) by -33.5 ± 7.0%, and the minimum SUV (SUV_min) by -54.4 ± 11.5% (P < .05). For shoulder tumors, SUV_max was reduced by -14.7 ± 7.5%, SUV_avg by -12.6 ± 6.3, and SUV_min by -30.3 ± 16.7% (P < .05). Capan-1 cells, which do not respond to cyclopamine, did not show significant SUV changes. CONCLUSIONS: The new generations of clinically implemented PET-CT scanners with high-resolution reconstruction detect a minimal response of PCX to low-dose short-term cyclopamine therapy without changes in tumor size and offer potential for preclinical translational imaging.     

Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer

Objectives

Previous non–simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.

Methods

We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body ¹⁸F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.

Results

92 lesions were detected. We found a significant inverse correlation between SUV_max and ADC_min (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUV_mean and ADC_min (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUV_max and ADC_min (r = -0.747, p = 0.002) and SUV_mean and ADC_min (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05).

Conclusions

Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

Key Point 1

This study investigates the correlation of functional parameters in a simultaneous PET/MRI.

Key Point 2

We found significant inverse correlations between ADC and SUV in cervical carcinoma which could increase knowledge about tumor biology.     

Detection of Vulnerable Atherosclerotic Plaque and Prediction of Thrombosis Events in a Rabbit Model Using 18F-FDG -PET/CT

Background

Detection of vulnerable plaques could be clinically significant in the prevention of cardiovascular events. We aimed to compare Fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) uptake in vulnerable and stable plaques, and investigate the feasibility of predicting thrombosis events using Positron Emission Tomography/Computed Tomography (PET/CT) angiography.

Methods

Atherosclerosis was induced in 23 male New Zealand white rabbits. The rabbits underwent pharmacological triggering to induce thrombosis. A pre-triggered PET/CTA scan and a post-triggered PET/CTA scan were respectively performed. ¹⁸F-FDG uptake by the aorta was expressed as maximal standardized uptake value (SUV_max) and mean SUV (SUV_mean). SUVs were measured on serial 7.5 mm arterial segments.

Results

Thrombosis was identified in 15 of 23 rabbits. The pre-triggered SUV_mean and SUV_max were 0.768±0.111 and 0.804±0.120, respectively, in the arterial segments with stable plaque, and 1.097±0.189 and 1.229±0.290, respectively, in the arterial segments with vulnerable plaque (P<0.001, respectively). The post-triggered SUV_mean and SUV_max were 0.849±0.167 and 0.906±0.191, respectively in the arterial segments without thrombosis, and 1.152±0.258 and 1.294±0.313, respectively in the arterial segments with thrombosis (P<0.001, respectively). The values of SUV_mean in the pre-triggered arterial segments were used to plot a receiver operating characteristic curve (ROC) for predicting thrombosis events. Area under the curve (AUC) was 0.898. Maximal sensitivity and specificity (75.4% and 88.5%, respectively) were obtained when SUV_mean was 0.882.

Conclusions

Vulnerable and stable plaques can be distinguished by quantitative analysis of ¹⁸F-FDG uptake in the arterial segments in this rabbit model. PET/CT may be used for predicting thrombosis events and risk-stratification in patients with atherosclerotic disease.     

Optimal reconstruction matrix and PET image filtration for point-spread function and time-of-flight reconstruction – A phantom study

IntroductionThe aim of this study was to determine the optimal image matrix and half-width of the Gaussian filter after iterative reconstruction of the PET image with point-spread function (PSF) and time-of-flight (TOF) correction, based on measuring the recovery coefficient (RC) curves. The measured RC curves were compared to those from an older system which does not use PSF and TOF corrections.Materials and methodsThe measurements were carried out on a NEMA IEC Body Phantom. We measured the RC curves based on SUV_max and SUV_A50 in source spheres with different diameters. The change in noise level for different reconstruction parameter settings and the relation between RC curves and the administered activity were also evaluated.ResultsWith an increasing size of image matrix and reduction in the half-width of the post-reconstruction Gaussian filter, there was a significant increase in image noise and overestimation of the SUV. The local increase in SUV, observed for certain filtrations and objects with a diameter below 13 mm, was caused by PSF correction. The decrease in administered activity, while maintaining the same conditions of acquisition and reconstruction, also led to overestimation of readings of the SUV and additionally to deterioration in reproducibility.ConclusionThis study proposes a suitable size for the image matrix and filtering for displaying PET and SUV measurements. The benefits were demonstrated as improved image parameters for the newer instrument, these even being found using relatively strong filtration of the reconstructed images.     

Respiratory Motion Reduction in PET/CT Using Abdominal Compression for Lung Cancer Patients

Purpose

Respiratory motion causes substantial artifacts in reconstructed PET images when using helical CT as the attenuation map in PET/CT imaging. In this study, we aimed to reduce the respiratory artifacts in PET/CT images of patients with lung tumors using an abdominal compression device.

Methods

Twelve patients with lung cancer located in the middle or lower lobe of the lung were recruited. The patients were injected with 370 MBq of ¹⁸F-FDG. During PET, the patients assumed two bed positions for 1.5 min/bed. After conducting free-breathing imaging, we obtained images of the patients with abdominal compression by applying the same setup used in the free-breathing scan. The differences in the standardized uptake value (SUV)_max, SUV_mean, tumor volume, and the centroid of the tumors between PET and various CT schemes were measured.

Results

The SUV_max and SUV_mean derived from PET/CT imaging using an abdominal compression device increased for all the lesions, compared with those obtained using the conventional approach. The percentage increases were 18.1% ±14% and 17% ±16.8% for SUV_max and SUV_mean, respectively. PET/CT imaging combined with abdominal compression generally reduced the tumor mismatch between CT and the corresponding attenuation corrected PET images, with an average decrease of 1.9±1.7 mm over all the cases.

Conclusions

PET/CT imaging combined with abdominal compression reduces respiratory artifacts and PET/CT misregistration, and enhances quantitative SUV in tumor. Abdominal compression is easy to set up and is an effective method used in PET/CT imaging for clinical oncology, especially in the thoracic region.     

Deformation Effect on SUVmax Changes in Thoracic Tumors Using 4-D PET/CT Scan

Respiratory motion blurs the standardized uptake value (SUV) and leads to a further signal reduction and changes in the SUV maxima. 4D PET can provide accurate tumor localization as a function of the respiratory phase in PET/CT imaging. We investigated thoracic tumor motion by respiratory 4D CT and assessed its deformation effect on the SUV changes in 4D PET imaging using clinical patient data. Twelve radiation oncology patients with thoracic cancer, including five lung cancer patients and seven esophageal cancer patients, were recruited to the present study. The 4D CT and PET image sets were acquired and reconstructed for 10 respiratory phases across the whole respiratory cycle. The optical flow method was applied to the 4D CT data to calculate the maximum displacements of the tumor motion in respiration. Our results show that increased tumor motion has a significant degree of association with the SUV_max loss for lung cancer. The results also show that the SUV_max loss has a higher correlation with tumors located at lower lobe of lung or at lower regions of esophagus.     

Identification of Metabolic Biomarkers Using Serial 18F–FDG PET/CT for Prediction of Recurrence in Advanced Epithelial Ovarian Cancer

PURPOSE. To evaluate the prognostic value of metabolic parameters derived from serial ¹⁸F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with advanced epithelial ovarian cancer (EOC). METHODS. Thirteen patients with advanced EOC who received surgical staging and adjuvant platinum-based combination chemotherapy were prospectively enrolled. ¹⁸F–FDG PET/CT was performed before and after the surgical staging, and after third cycle of chemotherapy. Tumor glucose metabolism at baseline and its change after operation and third cycle of chemotherapy such as changes of maximum standardized uptake values (ΔSUV_max) via ¹⁸F–FDG PET/CT were measured, and assessed regarding their ability to predict recurrence. RESULTS. Median duration of progression-free survival (PFS) was 25 months (range, 13–34), and although optimal debulking was performed in 10 patients, 5 (38.5%) patients experienced recurrence. Univariate analyses showed significant associations between recurrence and low ΔSUV_max after surgical staging, and low SUV_max change after third cycle of chemotherapy. Multivariate analysis identified low ΔSUV_max after third cycle of chemotherapy as an independent risk factor for recurrence (P = .047, hazard ratio (HR) 16.375, 95% CI 1.041–257.536). Kaplan–Meier survival curves showed that PFS significantly differed in groups categorized based on ΔSUV_max after chemotherapy (P = .001, log-rank test). CONCLUSIONS. ¹⁸F–FDG PET/CT allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after chemotherapy. The metabolic response measured as ΔSUV_max after third cycle of chemotherapy appears to be promising predictor of recurrence in patients with advanced EOC.     

Accuracy of target delineation by positron emission tomography-based auto-segmentation methods after deformable image registration: A phantom study

PurposeDiagnostic positron emission tomography and computed tomography (PET/CT) images can be fused to the planning CT images by a deformable image registration (DIR). The aim of this study was to evaluate the standardized uptake value (SUV) and target delineation on deformed PET images.MethodsWe used a cylindrical phantom and removable inserts of four spheres (16–38 mm in diameter) and three ellipsoids with a volume equal to the 38-mm-diameter sphere (S38) in each. S38 was filled with 18F-fluorodeoxyglucose activity, and then PET/CT images were acquired. The contours of S38 were generated using original PET images by PET auto-segmentation (PET-AS) methods of (1) SUV2.5, (2) 40% of maximum SUV (SUV40%max), and (3) gradient-based (GB), and were deformed to the other inserts by DIR. We compared the volumes and the SUV_max with the generated contours using the deformed PET images.ResultsThe SUV_max was slightly decreased by DIR; the mean absolute difference was −0.10 ± 0.04. For SUV2.5 and SUV40%max, the differences in S38 volumes between the original and deformed PET images were less than 5%, regardless of deformation type. For the GB, the contoured volumes obtained from deformed PET images were larger than those of the original PET images for the deformation type of ellipsoids. When the S38 was deformed to the 16-mm-diameter sphere, the maximum volume difference was −22.8%.ConclusionsAlthough SUV fluctuations by DIR were negligible, the target delineation on deformed PET images by the GB should be carefully considered owing to the distortion of intensity profiles.     

Effects of Reusing Baseline Volumes of Interest by Applying (Non-)Rigid Image Registration on Positron Emission Tomography Response Assessments

Objectives

Reusing baseline volumes of interest (VOI) by applying non-rigid and to some extent (local) rigid image registration showed good test-retest variability similar to delineating VOI on both scans individually. The aim of the present study was to compare response assessments and classifications based on various types of image registration with those based on (semi)-automatic tumour delineation.

Methods

Baseline (n = 13), early (n = 12) and late (n = 9) response (after one and three cycles of treatment, respectively) whole body [¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) scans were acquired in subjects with advanced gastrointestinal malignancies. Lesions were identified for early and late response scans. VOI were drawn independently on all scans using an adaptive 50% threshold method (A50). In addition, various types of (non-)rigid image registration were applied to PET and/or CT images, after which baseline VOI were projected onto response scans. Response was classified using PET Response Criteria in Solid Tumors for maximum standardized uptake value (SUV_max), average SUV (SUV_mean), peak SUV (SUV_peak), metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and the area under a cumulative SUV-volume histogram curve (AUC).

Results

Non-rigid PET-based registration and non-rigid CT-based registration followed by non-rigid PET-based registration (CTPET) did not show differences in response classifications compared to A50 for SUV_max and SUV_peak,, however, differences were observed for MATV, SUV_mean, TLG and AUC. For the latter, these registrations demonstrated a poorer performance for small lung lesions (<2.8 ml), whereas A50 showed a poorer performance when another area with high uptake was close to the target lesion. All methods were affected by lesions with very heterogeneous tracer uptake.

Conclusions

Non-rigid PET- and CTPET-based image registrations may be used to classify response based on SUV_max and SUV_peak. For other quantitative measures future studies should assess which method is valid for response evaluations by correlating with survival data.     

Réduction des effets de la respiration en imagerie TEP pulmonaire par une acquisition synchronisée à la respiration associée à une TDM en apnée

Respiratory motion causes a spread of lesion uptake over a larger area in Positron Emission Tomography (PET) images for moving structures. When CT images are used for attenuation correction of emission data, this motion may alter the quantization of PET images. We present the clinical results of a respiratory-gated PET processing “CT-based” method, which aims to improve PET-CT coregistration by using an additional breath-hold CT (BH-CT). The CT-based protocol consisted in a 10-min List Mode respiratory-gated PET acquisition, followed by an end-expiration BH-CT acquisition. During these two examinations, the respiratory signal was recorded continuously. Eleven pulmonary lesions were studied. Patients underwent both a standard clinical PET protocol (free breathing) and the CT-based protocol. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions’ centroids on PET and CT images. SUV_MAX (Standardized Uptake Value) and volume variations were also investigated. The CT-based method showed a significant reduction (p = 0.049) of centroid distances (mean relative change versus standard method: 49%). We also noted a higher SUV_MAX (mean change: 39%). Lesion volumes were significantly lower (p = 0.026) in CT-based PET volumes (mean change: 43%) compared with standard ones. The CT-based method improves PET-CT coregistration of pulmonary lesions. This protocol should lead to more accurate attenuation correction and thus improve SUV measurement.     

Valeur pronostique de la TEP/TDM dans le bilan initial du cancer du col utérin : SUVmax de la tumeur primitive et stadification ganglionnaire

PurposeWe investigated the prognostic significance of F-18 fluorodeoxyglucose (FDG) uptake measured as maximum Standardized Uptake Value (SUV_max) in primary tumor by positron emission tomography/computed tomography (PET/CT) in cervical cancer. The secondary objective was to determine the accuracy of the PET/CT for detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastases.MethodsThis retrospective study included 49 consecutive patients with stage IB1 to IVB cervical cancer. Univariate analysis was performed to determine the relationships between SUV_max value and pathological prognostics factors. Survival was estimated by Kaplan-Meier method. The gold standard of LN metastases was histologic.ResultsA significant difference in SUV_max was observed between stage I and stage II, stage I and stage IV and tumor size ≤ 4 cm and > 4 cm (P = 0.0001). There was a significant correlation between the SUV_max and tumor maximal size (r = 0.597) (P < 0.0001). PLN metastasis was found to be predictive of progression-free survival (P = 0.0007). The negative predictive value (NPV) of the PET/CT for PALN was 100% for locally advanced cervical carcinoma in 24 patients. The specificity and NPV of the PET/CT for PLN in eight early-stage cervical cancer were 100% and 87.5% (7/8) respectively. The PET/CT false-negative PLN measured less than 2 mm.ConclusionOur results demonstrate a correlation between SUV_max and tumor maximal size, which represents an indicator of tumor aggressiveness. PET/CT is effective to predict the absence of PALN in locally advanced cervical carcinoma. PET/CT is not sufficient to predict PLN in early-stage cancer without lymphadenectomy.     

Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice

Purpose

The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three ⁶⁸Ga-DOTA-labeled somatostatin analogues (⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC, and ⁶⁸Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts.

Methods

The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). ⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC, and ⁶⁸Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUV_max of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (V_t) was determined.

Results

Hepatic SUV_max and V_t were significantly higher with ⁶⁸Ga-DOTANOC than with ⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTATATE. No significant differences between tracers were found for SUV_max in tumor or muscle. No differences were found in the T/L SUV ratio between ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC, both of which had a higher fraction than ⁶⁸Ga-DOTANOC. The T/M SUV ratio was significantly higher with ⁶⁸Ga-DOTATATE than with ⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTANOC. The V_t for tumor was higher with ⁶⁸Ga-DOTATATE than with ⁶⁸Ga-DOTANOC and relatively similar to that of ⁶⁸Ga-DOTATOC.

Conclusions

This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although V_t was relatively similar with ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC, uptake was higher with ⁶⁸Ga-DOTATATE in the tumor than with ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATOC, suggesting a higher diagnostic value of ⁶⁸Ga-DOTATATE for detecting meningiomas.     

Multimodality Imaging to Predict Response to Systemic Treatment in Patients with Advanced Colorectal Cancer

Aim

Aim of this study was to investigate the potential of ¹⁸F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated.

Methods

Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. ¹⁸F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response.

Results

Pretreatment, high SUV_max, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUV_max and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment.

Conclusion

Pretreatment SUV_max, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and ¹⁸F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.     

Determination of an Optimal Standardized Uptake Value of Fluorodeoxyglucose for Positron Emission Tomography Imaging to Assess Pathological Volumes of Cervical Cancer: A Prospective Study

Purpose

To determine the optimal standardized uptake value (SUV) of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTV_PET) best matches with the pathological volume (GTV_PATH) in the cervical cancer.

Materials and Methods

Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTV_PATH calculated. The GTV_PET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTV_PET best matched with the GTV_PATH.

Results

An average of 85±10% shrinkage of tissue was observed after the formalin fixation. The GTV_PATH was 13.38±2.80 cm³ on average. The optimal threshold on percentile SUV and absolute SUV were 40.50%±3.16% and 7.45±1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTV_PATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUV_max (p<0.05).

Conclusion

The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTV_PATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion.     

Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy

 

The most common semiquantitative method of evaluation of pulmonary lesions using ¹⁸F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules.

Methods

Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUV_max for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUV_max cutoff of 2.5.

Results

The linear regression equations and (R²)s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm) are plotted in a dot diagram using an SUV_max cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUV_max cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1–2.0 cm); 94%, 23%, and 76%, respectively for group 3 (2.1–3.0 cm); and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUV_max cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules.

Conclusion

The slope of the regression line is greater for malignant than for benign nodules. Although, the SUV_max cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of small pulmonary nodules (≤ 1.0 cm).     

PET textural features stability and pattern discrimination power for radiomics analysis: An “ad-hoc” phantoms study

PurposeThe analysis of PET images by textural features, also known as radiomics, shows promising results in tumor characterization. However, radiomic metrics (RMs) analysis is currently not standardized and the impact of the whole processing chain still needs deep investigation. We characterized the impact on RM values of: i) two discretization methods, ii) acquisition statistics, and iii) reconstruction algorithm. The influence of tumor volume and standardized-uptake-value (SUV) on RM was also investigated.MethodsThe Chang-Gung-Image-Texture-Analysis (CGITA) software was used to calculate 39 RMs using phantom data. Thirty noise realizations were acquired to measure statistical effect size indicators for each RM. The parameter η² (fraction of variance explained by the nuisance factor) was used to assess the effect of categorical variables, considering η² < 20% and 20% < η² < 40% as representative of a “negligible” and a “small” dependence respectively. The Cohen’s d was used as discriminatory power to quantify the separation of two distributions.ResultsWe found the discretization method based on fixed-bin-number (FBN) to outperform the one based on fixed-bin-size in units of SUV (FBS), as the latter shows a higher SUV dependence, with 30 RMs showing η² > 20%. FBN was also less influenced by the acquisition and reconstruction setup: with FBN 37 RMs had η² < 40%, only 20 with FBS. Most RMs showed a good discriminatory power among heterogeneous PET signals (for FBN: 29 out of 39 RMs with d > 3).ConclusionsFor RMs analysis, FBN should be preferred. A group of 21 RMs was suggested for PET radiomics analysis.     

Fine needle aspiration outcomes of masses detected by positron emission tomography: correlation with standard uptake value

OBJECTIVES: To characterize the cytopathologic outcome of lesions detected on positron emission tomography (PET) scan. STUDY DESIGN: Cases with fine needle aspiration (FNA) performed because of a PET-positive lesion over an 18-month period were reviewed. Correlation with the standard uptake value (SUV) (using 2.5 as a cutoff value) was carried out. RESULTS: A total of 112 FNAs were found, of which 83 had adequate tissue for evaluation and available corresponding SUVs to be included in the final study. Fisher's exact test was carried out for correlation between FNA diagnosis and SUV Sixty-one (73.5%) lesions had an SUV > or = 2.5, 53 (87%) ofwhich were malignant and 8 (13%) benign on cytology. Twenty-two (26.5%) lesions had an SUV < 2.5, of which 12 (54.5%) showed benign and 10 (45.5%) showed malignant cytology. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of SUV were 84%, 60%, 87%, 56% and 78%, respectively. CONCLUSION: Our data show that FNA procedures performed for PET-positive lesions have high PPV, but low NPV. Therefore interpretation of PET SUV values < 2.5 as benign should be made with extreme caution.     

TIGAR Is Correlated with Maximal Standardized Uptake Value on FDG-PET and Survival in Non-Small Cell Lung Cancer

Objective

Evaluation of ¹⁸F-FDG uptake value via PET is central to current methods of diagnosis and staging of non-small cell lung cancer (NSCLC) due to its ability to evaluate expression levels of key regulators associated with glucose metabolism in tumor cells. Tp53-induced glycolysis and apoptosis regulator (TIGAR) is an important P53-induced protein that can inhibit glycolysis; however, there have been few clinical studies on its mechanism. Here we have investigated the relationship between TIGAR expression and ¹⁸F-FDG PET in tumors, along with its relationship with the clinical characteristics of NSCLC.

Methods

We analyzed SUV_max in 79 patients with NSCLC through immunohistochemical staining of TIGAR and five other biological markers associated with tumor cell glycolysis, in order to evaluate the correlation between their expression and SUV_max. We also plotted Kaplan-Meier survival curves to assess TIGAR expression with the prognosis and survival of patients with NSCLC.

Results

The key findings were as follows: SUV_max was negatively correlated with the expression of TIGAR (r = −0.31, p<0.01); TIGAR expression was correlated with tumor size (p = 0.01), histological type (p<0.01), differentiation degree (p<0.01) and lymph node metastasis(p<0.01) in patients with NSCLC; and the survival time of patients whose TIGAR was negatively expressed was significantly shorter than for those whose TIGAR was positively expressed (P = 0.023).

Conclusions

The expression of TIGAR in primary tumors is significantly correlated with SUV_max, and low expression of TIGAR may predict a worse clinical outcome in patients with NSCLC.     

Multicenter study of quantitative PET system harmonization using NIST-traceable 68Ge/68Ga cross-calibration kit

PurposeThe present study aimed to define the errors in SUV and demonstrate the feasibility of SUV harmonization among contemporary PET/CT scanners using a novel National Institute of Standards and Technology (NIST)-traceable ⁶⁸Ge/⁶⁸Ga source as the reference standard.MethodsWe used ⁶⁸Ge/⁶⁸Ga dose calibrator and PET sources made with same batch of ⁶⁸Ge/⁶⁸Ga embedded in epoxy that is traceable to the NIST standard. Bias in the amount of radioactivity and the radioactive concentrations measured by the dose calibrators and PET/CT scanners, respectively, was determined at five Japanese sites. We adjusted optimal dial setting of the dose calibrators and PET reconstruction parameters to close the actual amount of radioactivity and the radioactive concentration, respectively, of the NIST-traceable ⁶⁸Ge/⁶⁸Ga sources to harmonize SUV. Errors in SUV before and after harmonization were then calculated at each site.ResultsThe average bias in the amount of radioactivity and the radioactive concentrations measured by dose calibrator and PET scanner was −4.94% and −12.22%, respectively, before, and −0.14% and −4.81%, respectively, after harmonization. Corresponding averaged errors in SUV measured under clinical conditions were underestimated by 7.66%, but improved by −4.70% under optimal conditions.ConclusionOur proposed method using an NIST-traceable ⁶⁸Ge/⁶⁸Ga source identified bias in values obtained using dose calibrators and PET scanners, and reduced SUV variability to within 5% across different models of PET scanners at five sites. Our protocol using a standard source has considerable potential for harmonizing the SUV when contemporary PET scanners are involved in multicenter studies.