The Usefulness of Standardized Uptake Value in Differentiation between Benign and Malignant Thyroid Lesions Detected Incidentally in 18F-FDG PET/CT Examination

Introduction

In the last decade, (18)F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET and PET/CT) has become one of the major diagnostic tools used in oncology. A significant number of patients who undergo this procedure, due to non-thyroidal reasons, present incidental uptake of (¹⁸F-FDG) in the thyroid. The aim of the study was to compare the SUV_max (standardized uptake value) of thyroid focal lesions, which were incidentally found on PET/CT, in relation to the results of thyroid fine-needle aspiration biopsy (FNAB) and/or histopathological evaluation.

Materials and Methods

Patients referred for PET/CT examination, due to non-thyroidal illness, presented focal ¹⁸F-FDG uptake in the thyroid and were advised to undergo ultrasonography (US), hormonal evaluation, FNAB and/or total thyroidectomy at our institution.

Results

6614 PET/CT examinations performed in 5520 patients were analyzed. Of the 122 patients with focal thyroid ¹⁸F-FDG activity, 82 patients (67.2%) underwent further thyroid evaluation using FNAB. Benign lesions were diagnosed in 46 patients, malignant - in 19 patients (confirmed by post-surgical histopathology), while 17 patients had inconclusive results of cytological assessment. Mean SUV_max of benign lesions was 3.2±2.8 (median = 2.4), while the mean SUV_max value for malignant lesions was 7.1±8.2 (median = 3.5). The risk of malignancy was 16.7% for lesions with a SUV_max under 3, 43.8% for lesions with a SUV_max between 3 and 6, and 54.6% for lesions with a SUV_max over 6. In the group of malignant lesions, a positive correlation between the lesion’s diameter and SUV_max was observed (p = 0.03, r = 0.57).

Conclusions

Subjects with incidental focal uptake of ¹⁸F-FDG in thyroid are at a high risk of thyroid malignancy. A high value of SUV_max further increases the risk of malignancy, indicating the necessity for further cytological or histological evaluation. However, as SUV_max correlated with the diameter of malignant lesions, small lesions with focal uptake of ¹⁸F-FDG should be interpreted cautiously.     

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.     

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.     

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.     

Prognostic Value of 18F-FDG PET/CT in Surgical Non-Small Cell Lung Cancer: A Meta-Analysis

Background

The identification of surgical non-small cell lung cancer (NSCLC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. This meta-analysis explored the prognostic value of maximal standardized uptake value (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients.

Materials and Methods

MEDLINE, EMBASE and Cochrane Libraries were systematically searched until August 1, 2015. Prospective or retrospective studies that evaluated the prognostic roles of preoperative 18F-FDG PET/CT with complete DFS and OS data in surgical NSCLC patients were included. The impact of SUV_max, MTV or TLG on survival was measured using hazard ratios (HR). Sub-group analyses were performed based on disease stage, pathological classification, surgery only and cut-off values.

Results

Thirty-six studies comprised of 5807 patients were included. The combined HRs for DFS were 2.74 (95%CI 2.33–3.24, unadjusted) and 2.43 (95%CI: 1.76–3.36, adjusted) for SUV_max, 2.27 (95%CI 1.77–2.90, unadjusted) and 2.49 (95%CI 1.23–5.04, adjusted) for MTV, and 2.46 (95%CI 1.91–3.17, unadjusted) and 2.97 (95%CI 1.68–5.28, adjusted) for TLG. The pooled HRs for OS were 2.54 (95%CI 1.86–3.49, unadjusted) and 1.52 (95%CI 1.16–2.00, adjusted) for SUV_max, 2.07 (95%CI 1.16–3.69, unadjusted) and 1.91 (95%CI 1.13–3.22, adjusted) for MTV, and 2.47 (95%CI 1.38–4.43, unadjusted) and 1.94 (95%CI 1.12–3.33, adjusted) for TLG. Begg’s test detected publication bias, the trim and fill procedure was performed, and similar HRs were obtained. The prognostic role of SUV_max, MTV and TLG remained similar in the sub-group analyses.

Conclusions

High values of SUV_max, MTV and TLG predicted a higher risk of recurrence or death in patients with surgical NSCLC. We suggest the use of FDG PET/CT to select patients who are at high risk of disease recurrence or death and may benefit from aggressive treatments.     

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.     

Construction and Evaluation of Quantitative Small-Animal PET Probabilistic Atlases for [18F]FDG and [18F]FECT Functional Mapping of the Mouse Brain

Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([¹⁸F]FDG) and dopamine transporter ([¹⁸F]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [¹⁸F]FDG and [¹⁸F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice.

Methods

Twenty-three adult C57BL6 mice were scanned with [¹⁸F]FDG and [¹⁸F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [¹⁸F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMR_glc), using (2) standardized uptake values (SUV_glc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [¹⁸F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination.

Results

Registration accuracy was between 0.21–1.11 mm. Regional intersubject variabilities of cMR_glc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [¹⁸F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMR_glc positively correlated to SUV_glc measured within the 45–60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT availability.

Conclusion

MRM-based small-animal PET templates facilitate accurate assessment and spatial localization of mouse brain function using VOI or voxel-based analysis. Regional intersubject- and test-retest variations indicate that for these targets accuracy comparable to humans can be achieved.     

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.     

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.     

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.     

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.     

Differences between TNM classification and 2-[18F]FDG PET parameters of primary tumor in NSCLC patients

BackgroundThe aim of the study was to compare the TNM classification with 2-[¹⁸F]FDG PE T biological parameters of primary tumor in patients with NSCLC.Materials and methodsRetrospective analysis was performed on a group of 79 newly diagnosed NSCLC patients. PET scans were acquired on Gemini TF PET/CT scanner 60–70 min after injection of 2-[¹⁸F]FDG with the mean activity of 364 ± 75 MBq, with the area being examined from the vertex to mid-thigh. The reconstructed PET images were evaluated using MIM 7.0 Software for SUV_max, MTV and TLG values.ResultsThe analysis of the cancer stage according to TNM 8^th edition showed stage IA2 in 8 patients, stage IA3 — 6 patients, stage IB — 4 patients, IIA — 3 patients, 15 patients with stage IIB, stage IIIA — 17 patients, IIIB — 5, IIIC — 5, IVA in 7 patients and stage IVB in 9 patients. The lowest TLG values of primary tumor were observed in stage IA2 (11.31 ± 15.27) and the highest in stage IIIC (1003.20 ± 953.59). The lowest value of primary tumor in SUV_max and MTV were found in stage IA2 (6.8 ± 3.8 and 1.37 ± 0.42, respectively), while the highest SUV_max of primary tumor was found in stage IIA (13.4 ± 11.4) and MTV in stage IIIC (108.15 ± 127.24).ConclusionTNM stages are characterized by different primary tumor 2-[¹⁸F]FDG PET parameters, which might complement patient outcome.     

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.     

[18F]-Fluorodeoxyglucose Positron Emission Tomography Can Contribute to Discriminate Patients with Poor Prognosis in Hormone Receptor-Positive Breast Cancer

Background

Patients with hormone receptor-positive breast cancer typically show favorable survival. However, identifying individuals at high risk of recurrence among these patients is a crucial issue. We tested the hypothesis that [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans can help predict prognosis in patients with hormone receptor-positive breast cancer.

Methods

Between April 2004 and December 2008, 305 patients with hormone receptor-positive breast cancer who underwent FGD-PET were enrolled. Patients with luminal B subtype were identified by positivity for human epidermal growth factor receptor-2 (HER2) or high Ki67 (≥14%) according to criteria recently recommended by the St. Gallen panelists. The cut-off value of SUV_max was defined using the time-dependent receiver operator characteristic curve for recurrence-free survival (RFS).

Results

At a median follow up of 6.23 years, continuous SUV_max was a significant prognostic factor with a hazard ratio (HR) of 1.21 (p = 0.021). The cut-off value of SUV_max was defined as 4. Patients with luminal B subtype (n = 82) or high SUV_max (n = 107) showed a reduced RFS (p = 0.031 and 0.002, respectively). In multivariate analysis for RFS, SUV_max carried independent prognostic significance (p = 0.012) whereas classification with immunohistochemical markers did not (p = 0.274). The Harell c-index was 0.729. High SUV_max was significantly associated with larger tumor size, positive nodes, HER2 positivity, high Ki67 (≥14%), high tumor grade, and luminal B subtype.

Conclusions

Among patients with hormone receptor-positive breast cancer, FDG-PET can help discriminate patients at high risk of tumor relapse.     

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.     

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

Objective

Inflammation is an important contributor to atherosclerosis progression. A glucose analogue ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [¹⁸F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [¹⁸F]FDG to various stages of coronary plaques in a pig model.

Methods

First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [¹⁸F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).

Results

Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [¹⁸F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).

Conclusions

We found increased uptake of [¹⁸F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [¹⁸F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.     

Serum VEGF levels as predictive marker of bisphosphonate-related osteonecrosis of the jaw

This study was aimed to investigate the significance of ¹⁸F-FDG PET/CT in secondary hemophagocytic lymphohistiocytosis (sHLH) patients. A total of 18 patients received ¹⁸F-FDG PET/CT scan at initial diagnosis. All patients (18/18) had at least 3 organs involved, with increased FDG metabolism in different degrees. Fifteen cases (15/18) had definite underlying diseases, including infections (IAHLH), rheumatosis (RAHLH), or malignancy (MAHLH). The SUV_max of patients in MAHLH group was significantly higher than patients in IAHLH group or RAHLH group (P?=?0.015, P?=?0.045). Furthermore, the SUV_max of patients in IAHLH group was significantly higher than patients of RAHLH group (P?=?0.043). Therefore, we concluded that ¹⁸F-FDG PET/CT may especially play important role in differential diagnosis of sHLH.     

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).