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.     

Correlation of the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in Lymph Node Metastases of Non-Small Cell Lung Cancer (NSCLC) Patients Using Hybrid 18F-FDG PET/MRI

ObjectiveTo compare the apparent diffusion coefficient (ADC) in lymph node metastases of non-small cell lung cancer (NSCLC) patients with standardized uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).ResultsA total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUV_max was 9.1 ± 3.8 and mean SUV_mean was 6.0 ± 2.5 while mean ADC_mean was 877.0 ± 128.6 x10^-5 mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUV_max and ADC_mean as well as SUV_mean and ADC_mean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed.ConclusionThe present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.     

Comparison of Methods to Reduce Myocardial 18F-FDG Uptake in Mice: Calcium Channel Blockers versus High-Fat Diets

Purpose

Besides its application in oncology, ¹⁸F-FDG PET-CT imaging is also useful in the diagnosis of certain lung infections, inflammatory diseases, and atherosclerotic plaques. Myocardial uptake of ¹⁸F-FDG may hamper visualization of the lesions caused by these diseases. Two approaches have been proposed for reducing myocardial uptake in preclinical studies, namely, calcium channel blockers (verapamil) and high-fat diets such as commercial ketogenic diets and sunflower seed diets. The objective of this study was to compare the efficacy of these approaches in reducing myocardial uptake of ¹⁸F-FDG in mice.

Methods

We performed two experiments. In experiment A, each animal underwent four ¹⁸F-FDG PET/CT scans in the following order: baseline, after administration of verapamil, after two days on ketogenic diet and after two days on sunflower seeds. PET scans were performed 60 minutes after injection of 18.5 MBq of ¹⁸F-FDG. In experiment B, the best protocol of the three (ketogenic diet) was evaluated in a lung inflammation model to assess the efficacy of reducing myocardial uptake of ¹⁸F-FDG.

Results

Compared with baseline (SUV 2.03±1.21); the greatest reduction in uptake of ¹⁸F-FDG was with ketogenic diet (SUV 0.79±0.16; p = 0.008), followed by sunflower seeds (SUV 0.91±0.13; p = 0.015); the reduction in myocardial uptake produced by verapamil was not statistically significant (SUV 1.78±0.79; p = NS). In experiment B, complete suppression of myocardial uptake noticeably improved the visualization of inflamed areas near the heart, while in the case of null or partial myocardial suppression, it was much harder to distinguish lung inflammation from myocardial spillover.

Conclusion

A high-fat diet appeared to be the most effective method for decreasing myocardial uptake of ¹⁸F-FDG in healthy mice, outperforming verapamil. Our findings also demonstrate that ketogenic diet actually improves visualization of inflammatory lesions near the heart.     

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.     

In Vivo Correlation of Glucose Metabolism,Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI

Objective

To demonstrate the feasibility of simultaneous acquisition of ¹⁸F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters.

Methods

17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous ¹⁸F-FDG-PET/MRI including DWI and T1w-DCE. SUV_max, SUV_mean, ADC_mean, ADC_min and K ^trans, k _ep and v _e were measured for each tumour and correlated using Spearman’s ρ.

Results

Significant correlations were observed between SUV_mean and K ^trans (ρ = 0.43; p ≤ 0.05); SUV_mean and k _ep (ρ = 0.44; p ≤ 0.05); K ^trans and k _ep (ρ = 0.53; p ≤ 0.05); and between k _ep and v _e (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUV_max and ADC_min (ρ = -0.35; p = 0.08); SUV_max and K ^trans (ρ = 0.37; p = 0.07); SUV_max and k _ep (ρ = 0.39; p = 0.06); and ADC_mean and v _e (ρ = 0.4; p = 0.06).

Conclusion

Simultaneous ¹⁸F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density.     

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.     

18F-FDG PET Metabolic Parameters and MRI Perfusion and Diffusion Parameters in Hepatocellular Carcinoma: A Preliminary Study

Objectives

Glucose metabolism, perfusion, and water diffusion may have a relationship or affect each other in the same tumor. The understanding of their relationship could expand the knowledge of tumor characteristics and contribute to the field of oncologic imaging. The purpose of this study was to evaluate the relationships between metabolism, vasculature and cellularity of advanced hepatocellular carcinoma (HCC), using multimodality imaging such as ¹⁸F-FDG positron emission tomography (PET), dynamic contrast enhanced (DCE)-MRI, and diffusion weighted imaging(DWI).

Materials and Methods

Twenty-one patients with advanced HCC underwent ¹⁸F-FDG PET, DCE-MRI, and DWI before treatment. Maximum standard uptake values (SUV_max) from ¹⁸F-FDG-PET, variables of the volume transfer constant (K^trans) from DCE-MRI and apparent diffusion coefficient (ADC) from DWI were obtained for the tumor and their relationships were examined by Spearman’s correlation analysis. The influence of portal vein thrombosis on SUV_max and variables of K^trans and ADC was evaluated by Mann-Whitney test.

Results

SUV_max showed significant negative correlation with K^trans _max (ρ = −0.622, p = 0.002). However, variables of ADC showed no relationship with variables of K^trans or SUV_max (p>0.05). Whether portal vein thrombosis was present or not did not influence the SUV _max and variables of ADC and K^trans (p>0.05).

Conclusion

In this study, SUV was shown to be correlated with K_trans in advanced HCCs; the higher the glucose metabolism a tumor had, the lower the perfusion it had, which might help in guiding target therapy.     

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.     

Different Prognostic Values of Plasma Epstein-Barr Virus DNA and Maximal Standardized Uptake Value of 18F-FDG PET/CT for Nasopharyngeal Carcinoma Patients with Recurrence

Purpose

To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUV_max ) of ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence.

Patients and Methods

A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with ¹⁸F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUV_max were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model.

Results

In the subgroup of patients with locoregional recurrence, patients with SUV_max<8.65 had significantly better overall survival (OS) (P=0.005) compared with the patients with SUV_max ≥8.65. However, both elevated EBV DNA load (≥21,100 copies/ml) and distant SUV_max (≥13.55) were significantly associated with worse OS compared with the patients with EBV DNA <21,100 copies/ml or distant SUV_max <13.55 for the subgroup with distant recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA was superior to that of SUV_max (P=0.062). Multivariate analysis showed that SUV_max was only an independent prognostic factor for OS in patients with locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for the patients with distant recurrence (P=0.007). For those patients with undetectable EBV DNA, SUV_max<8.65 was still an independent favorable prognostic factor (P=0.038).

Conclusions

SUV_max is a useful biomarker for predicting OS in nasopharyngeal carcinoma patients with locoregional recurrence or with undetectable EBV DNA. Both distant SUV_max and EBV DNA appear to be independent predictors of OS in patients with distant recurrence; however, the predictive ability of EBV DNA was superior to that of SUV_max.     

Correlation of Standardized Uptake Value and Apparent Diffusion Coefficient in Integrated Whole-Body PET/MRI of Primary and Recurrent Cervical Cancer

Background

To evaluate a potential correlation of the maximum standard uptake value (SUV_max) and the minimum apparent diffusion coefficient (ADC_min) in primary and recurrent cervical cancer based on integrated PET/MRI examinations.

Methods

19 consecutive patients (mean age 51.6 years; range 30–72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUV_max and into ADC parameter maps to determine ADC_min values. Pearson’s correlation coefficients were calculated to assess a potential correlation between the mean values of ADC_min and SUV_max.

Results

In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUV_max (12.5±6.5) and ADC_min (644.5±179.7×10⁻⁵ mm²/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = −0.342, p<0.05). When subdivided in primary and recurrent tumors, primary tumors and associated primary lymph node metastases revealed a significant and strong inverse correlation between SUV_max and ADC_min (R = −0.692, p<0.001), whereas recurrent cancer lesions did not show a significant correlation.

Conclusions

These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.     

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.     

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.     

A Virtual Clinical Trial of FDG-PET Imaging of Breast Cancer: Effect of Variability on Response Assessment

INTRODUCTION: There is growing interest in using positron emission tomography (PET) standardized uptake values (SUVs) to assess tumor response to therapy. However, many error sources compromise the ability to detect SUV changes. We explore relationships between these errors and overall SUV variability. METHODS: We used simulations in a virtual clinical trial framework to study impacts of error sources from scanning and analysis effects on assessment of SUV changes. We varied tumor diameter, scan duration, pretherapy SUV, magnitude of change in SUV, image reconstruction filter, and SUV metric. Poisson noise was added to the raw data before image reconstruction. Variance from global sources of error, e.g., scanner calibration, was incorporated. Two thousand independent noisy sinograms per scenario were generated and reconstructed. We used SUVs to create receiver operating characteristic (ROC) curves to quantify ability to assess response. Integrating area under the ROC curve summarized ability to detect SUV changes. RESULTS: Scan duration and image reconstruction method had relatively little impact on ability to measure response. SUV_MAX is nearly as effective as SUV_MEAN, especially with increased image smoothing and despite size-matched region of interest placement. For an effective variability of 15%, we found the Positron Emission Tomography Response Criteria in Solid Tumors criteria for measuring response (±30%) similar to the European Organization for Research and Treatment of Cancer criteria (±25%). CONCLUSIONS: For typical PET variance levels, tumor response must be 30% to 40% to be reliably determined using SUVs. PET scan duration and image reconstruction method had relatively little effect.     

Background Intestinal 18F-FDG Uptake Is Related to Serum Lipid Profile and Obesity in Breast Cancer Patients

Background

This study investigated the relationships between background intestinal uptake on ¹⁸F–FDG PET and cardio-metabolic risk (CMR) factors.

Methods

A total of 326 female patients that underwent ¹⁸F–FDG PET to determine the initial stage of breast cancer were enrolled. None of the patients had history of diabetes or hypertension. The background intestinal uptake on PET was visually graded (low vs. high uptake group) and quantitatively measured using the maximal standardized uptake value (SUV_max). SUV_max of 7 bowel segments (duodenum, jejunum, ileum, cecum, hepatic flexure, splenic flexure, and descending colon-sigmoid junction) were averaged for the total bowel (TB SUV_max). Age, body mass index (BMI), fasting blood glucose level (BST), triglyceride (TG), cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were the considered CMR factors. The relationships between background intestinal ¹⁸F–FDG uptake on PET and diverse CMR factors were analyzed.

Results

The visual grades based on background intestinal ¹⁸F–FDG uptake classified 100 (30.7%) patients into the low uptake group, while 226 (69.3%) were classified into the high uptake group. Among CMR factors, age (p = 0.004), BMI (p<0.001), and TG (p<0.001) were significantly different according to visual grade of background intestinal ¹⁸F–FDG uptake. Quantitative TB SUV_max showed significant positive correlation with age (r = 0.203, p<0.001), BMI (r = 0.373, p<0.001), TG (r = 0.338, p<0.001), cholesterol (r = 0.148, p = 0.008), and LDL (r = 0.143, p = 0.024) and significant negative correlation with HDL (r = -0.147, p = 0.022). Multivariate analysis indicated that BMI and TG were independent factors in both visually graded background intestinal ¹⁸F–FDG uptake (p = 0.027 and p = 0.023, respectively) and quantitatively measured TB SUV_max (p = 0.006 and p = 0.004, respectively).

Conclusion

Increased background intestinal ¹⁸F–FDG uptake on PET may suggest alteration of lipid metabolism and risk of cardio-metabolic disease in non-diabetic and non-hypertensive breast cancer patients.     

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.     

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).     

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.     

An Observational Study of Circulating Tumor Cells and 18F-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer

Introduction

We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by ¹⁸F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.

Materials & Methods

We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or “HD-CTCs”). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.

Results

We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0–3.6) and median maximum standardized uptake value (SUV_max) was 7.2 (IQR 3.7–15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUV_max (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUV_max or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.

Conclusions

CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.