Mean SUV Research Articles

Reducing Respiratory Motion-Induced Errors in PET and CT Using an Iterative Image-to-Image Reconstruction Algorithm

Respiratory motion may change SUVmax and SUVpeak in PET images and compromise target definition and treatment response assessment in radiation therapy. While 4D imaging techniques may help address these issues, the time required for 4D data acquisition, image reconstruction and administrative costs keep 3D PET imaging staying as the mainstream in clinical practice. The purpose of this study is to explore the potential of using 4DCT information to remove motion-induced errors in 3D PET/CT images. A novel iterative image-to-image (III) reconstruction algorithm was developed. Specifically, a motion-blurred PET image was considered as a weighted average of PET images acquired at different respiration phases. PET images at each phase were assumed to be deformed from a virtual reference image. Image-intensity-based B-Spline registrations were performed on 4DCT from the end-inhale to the other phases. Resultant deformation maps were used to establish a set of composition equations between the virtual reference image and the blurred PET image. A maximum likelihood estimation maximization (MLEM) algorithm was used to solve these equations. The solution of these equations was smoothed by minimizing total gradient variations before generating the virtual reference image. A 10-phase 4D dataset with the resolution of 3.64×3.64×3.24 for PET and1.37×1.37×2.15 for CT was acquired from a lung cancer patient and used to benchmark the computed results. Different from previous studies, the III-reconstruction was performed in the image space, so there is no any tracking device or sorting operation required during the PET image acquisition. For the blurred PET, III-reconstructed PET and PET0 (which is the 4D-PET at the end-inhale phase), their relative SUVpeak are 10.2, 12.7 and 12.8, and SUVmax are 9.2, 12.5 and 13.1. With PET0 taken as the baseline, the III-reconstruction reduced the motion-induced error from 20.3% to 0.8% for SUVpeak, and from 29.8% to 4.6% for SUVmax. The mean SUV difference between the III-reconstructed PET and PET0 was 1.8% in the tumor region, and 13.2% over the whole image domain. Large differences between the two PET images were located mainly in the chest wall where ribs were mis-registered about 6 mm due to discontinuous motion between the ribs and lungs. The III-reconstruction algorithm was also applied to the 4DCT image. Image contrast ratios for the blurred 3DCT, III-reconstructed CT, and CT0 are 1.8, 3.7 and 4.0, respectively. The III-reconstruction method can be used to correct motion-induced errors in SUVmax and SUVpeak and improve image contrasts in free-breathing PET and CT images. This method does not require sorting projection data, thereby reducing financing cost and clinical burden. Further investigation of this reconstruction method is warranted.

Assessment of acute bone loading in humans using [18F]NaF PET/MRI

PurposeThe acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [18F]-sodium fluoride ([18F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading.MethodsTwelve healthy subjects underwent two consecutive 50-min [18F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of KiNLR, K1, k2, k3, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUVmax were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone.ResultsExercise induced a significant (p < <0.001) increase in [18F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K1 and blood volume) increased, whereas the NaF extraction fraction [k3/(k2 + k3)] was reduced.ConclusionsBone loading induces an acute response in bone physiology as quantified by [18F]NaF PET kinetics. Dynamic imaging after bone loading using [18F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.

Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors.

To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET). Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis. Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS. ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

Abstract 5283: Prognostic value of resectable hepatocellular carcinoma: Clinico-pathologic findings

Abstract We investigated the prognostic factors of resectable hepatocellular carcinoma (HCC). Preoperative peripheral blood factors, fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and pathologic parameters were investigated for progression free survival (PFS). From February 2008 to December 2012, a retrospective analysis was conducted on 65 patients who had received liver resection. Peripheral blood parameters were collected within 7 days based on operation date. The 18F-FDG uptake was calculated based on the maximum standardized uptake value of the tumor (SUVmax), the liver mean SUV and the tumor-to-normal SUV ratio (TNR). Immuno-histochemical (IHC) stain results were reviewed by a pathologist through specimen. A total of 65 patients were included (46 males, 19 females; average age, 57.5 ± 8.9 years). The median PFS of HCC was 52.9 months. SUVmax was correlated with PFS and the optimal cut off value of SUVmax was 3.25 (p = 0.005). Median PFS of low SUVmax was 76.4 months and high SUVmax was 8.5 months. The optimal cut-off value of TNR was 1.77 for PFS. The median PFS of HCC in patients with low TNR (&amp;lt; 1.77) and high TNR (≥ 1.77) was 82.3 and 7.0 months, respectively (p = 0.002). AST to platelet ratio index (APRI) could be a predictable marker for recurrence of HCC (p = 0.034). The median PFS of high PNI and low PNI were 64.9 and 10.9 months, respectively (p = 0.004). The IHC expression of glucose uptake transporter 2 was correlated with SUVmax. Preoperative SUVmax, TNR, APRI and PNI could predict recurrence after curative resection of HCC. Citation Format: Jin Young Kim, Mi Hwa Heo, So Jin Shin. Prognostic value of resectable hepatocellular carcinoma: Clinico-pathologic findings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5283.

18F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer.

Anti-PD-1/PD-L1 blockade can restore tumour-specific T-cell immunity and is an emerging therapy in non-small-cell lung cancer (NSCLC). We investigated the correlation between 18F-FDG PET/CT-based markers and tumour tissue expression of PD-L1, necrosis and clinical outcome in patients receiving checkpoint inhibitor treatment. PD-Li expression in biopsy or resection specimens from 49 patients with confirmed NSCLC was investigated by immunohistochemistry. Maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were obtained from 18F-FDG PET/CT images. The ratio of metabolic to morphological lesion volumes (MMVR) and its association with PD-L1 expression in each lesion were calculated. The associations between histologically reported necrosis and 18F-FDG PET imaging patterns and radiological outcome (evaluated by iRECIST) following anti-PD-1/PD-L1 therapy were also analysed. In 14 patients, the association between necrosis and MMVR and tumour immune contexture were analysed by multiple immunofluorescent (IF) staining for CD8, PD-1, granzyme B (GrzB) and NFATC2. In total, 25 adenocarcinomas and 24 squamous cell carcinomas were analysed. All tumours showed metabolic 18F-FDG PET uptake. MMVR was correlated inversely with PD-L1 expression in tumour cells. Furthermore, PD-L1 expression and low MMVR were significantly correlated with clinical benefit. Necrosis was correlated negatively with MMVR. Multiplex IF staining showed a greater frequency of activated CD8+ cells in necrotic tumours than in nonnecrotic tumours in both stromal and epithelial tumour compartments. This study introduces MMVR as a new imaging biomarker and its ability to noninvasively capture increased PD-L1 tumour expression and predict clinical benefit from checkpoint blockade in NSCLC should be further evaluated.

Prediction of occult lymph node metastasis using SUV, volumetric parameters and intratumoral heterogeneity of the primary tumor in T1-2N0M0 lung cancer patients staged by PET/CT.

The aim of this study was to identify whether PET/CT-related metabolic parameters of the primary tumor could predict occult lymph node metastasis (OLM) in patients with T1-2N0M0 NSCLC staged by 18F-FDG PET/CT. 215 patients with clinical T1-2N0M0 (cT1-2N0M0) NSCLC who underwent both preoperative FDG PET/CT and surgical resection with the systematic lymph node dissection were included in the retrospective study. Heterogeneity factor (HF) was obtained by finding the derivative of the volume-threshold function from 40 to 80% of the maximum standardized uptake value (SUVmax). Univariate and multivariate stepwise logistic regression analyses were used to identify these PET parameters and clinicopathological variables associated with OLM. Statistically significant differences were detected in sex, tumor site, SUVmax, mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis and HF between patients with adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). OLM was detected in 36 (16.7%) of 215 patients (ADC, 27/152 = 17.8% vs. SQCC, 9/63 = 14.3%). In multivariate analysis, MTV (OR = 1.671, P = 0.044) in ADC and HF (OR = 8.799, P = 0.023) in SQCC were potent associated factors for the prediction of OLM. The optimal cutoff values of 5.12cm3 for MTV in ADC, and 0.198 for HF in SQCC were determined using receiver operating characteristic curve analysis. In conclusion, MTV was an independent predictor of OLM in cT1-2N0M0 ADC patients, while HF might be the most powerful predictor for OLM in SQCC. These findings would be helpful in selecting patients who might be considered as candidates for sublobar resection or new stereotactic ablative radiotherapy.

Assessing the Effect of Various Blood Glucose Levels on 18F-FDG Activity in the Brain, Liver, and Blood Pool.

Studies have extensively analyzed the effect of hyperglycemia on 18F-FDG uptake in normal tissues and tumors. In this study, we measured SUV in the brain, liver, and blood pool in normoglycemia, hyperglycemia, and hypoglycemia to understand the effect of blood glucose on 18F-FDG uptake and to develop a formula to correct SUV. Methods: Whole-body 18F-FDG PET/CT images of adults were selected for analysis. Brain SUVmax, blood-pool SUVmean, and liver SUVmean were measured at blood glucose ranges of 61-70, 71-80, 81-90, 91-100, 101-110, 111-120, 121-130, 131-140, 141-150, 151-160, 161-170, 171-180, 181-190, 191-200, and 201 mg/dL and above. At each blood glucose range, 10 PET images were analyzed (total, 150). The mean (±SD) SUV of the brain, liver, and blood pool at each blood glucose range was calculated, and blood glucose and SUV curves were generated. Because brain and tumors show a high expression of glucose transporters 1 and 3, we generated an SUV correction formula based on percentage reduction in brain SUVmax with increasing blood glucose level. Results: Mean brain SUVmax gradually decreased with increasing blood glucose level, starting after a level of 110 mg/dL. The approximate percentage reduction in brain SUVmax was 20%, 35%, 50%, 60%, and 65% at blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively. In the formula we generated, measured SUVmax is multiplied by a reduction factor of 1.25, 1.5, 2, 2.5, and 2.8 for the blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively, to correct SUV. Brain SUVmax did not differ between hypoglycemic and normoglycemic patients (P > 0.05). SUVmean in the blood pool and liver was lower in hypoglycemic patients (P < 0.05) and did not differ between hyperglycemic (P > 0.05) and normoglycemic patients. Conclusion: Hyperglycemia gradually reduces brain 18F-FDG uptake, starting after a blood glucose level of 110 mg/dL. Hyperglycemia does not affect 18F-FDG activity in the liver or blood pool. Hypoglycemia does not seem to affect brain 18F-FDG uptake but appears to reduce liver and blood-pool activity. The simple formula we generated can be used to correct SUV in hyperglycemic adults in selected cases.

Pilot study to enhance FDG-PET imaging of prostate cancers with the metabolic inhibitor ranolazine.

e16551 Background: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) is a widely-used imaging modality for many cancers; however, its utility in prostate cancer is limited. Fatty acid oxidation (FAO) is a primary source of energy for early prostate cancer. We previously demonstrated that FAO inhibition in prostate cancer mouse models resulted in increased glucose metabolism and enhanced tumor FDG uptake, with peak uptake at 24 hours. To validate these preclinical findings, we conducted a pilot study to evaluate whether a partial FAO inhibitor, ranolazine, increases tumor FDG uptake on PET imaging for prostate cancer. Methods: Prostate cancer patients with untreated localized cancer (arm 1) and with metastatic disease on hormonal or other therapy (arm 2) were enrolled and underwent baseline and post-treatment FDG-PET/CT scans (standard dose of 10 mCi FDG). Ranolazine 1000mg PO BID x 2 doses was given within 24-48 hours of the second scan. The primary objective was to evaluate the rate of successful enhancement of FDG uptake on PET imaging, based on one or more of the following criteria: 30% increase in maximum SUV with an absolute change of 2 units; 30% increase in mean SUV with an absolute change of 0.75 units; or 20% increase in mean SUV with an absolute change of 1 unit. Results: Eleven patients (four in arm 1, seven in arm 2) were enrolled. Ranolazine was well tolerated by all participants, with no adverse effects observed. Both increases and decreases in SUV uptake were observed on the post-ranolazine scans. No patient met the predefined criteria for successful enhancement of FDG uptake. There was an incidental finding of thyroid cancer seen in one patient that was discovered on PET imaging. The study was closed early due to the emerging clinical availability of alternative and effective PET imaging modalities such as [11C] choline, [18F] fluciclovine, [68Ga] PSMA, and [18F] sodium fluoride. Conclusions: Given the small sample size, we were not able to make any firm conclusions. In this limited study, ranolazine treatment did not result in enhanced FDG-PET-tumor detection. ClinicalTrials.gov identifier: NCT01992016. Supported by the William Meyn Foundation; NIH/NCI P30CA46934, 5K12CA086913, CA168934; ACS RSG-16-256-01-TBE; Colorado Translational Research Imaging Center Pilot Award; Paul Sandoval Cancer Research Summer Fellowship. Clinical trial information: NCT01992016.

Joint correction of attenuation and scatter in image space using deep convolutional neural networks for dedicated brain 18F-FDG PET

Dedicated brain positron emission tomography (PET) devices can provide higher-resolution images with much lower doses compared to conventional whole-body PET systems, which is important to support PET neuroimaging and particularly useful for the diagnosis of neurodegenerative diseases. However, when a dedicated brain PET scanner does not come with a combined CT or transmission source, there is no direct solution for accurate attenuation and scatter correction, both of which are critical for quantitative PET. To address this problem, we propose joint attenuation and scatter correction (ASC) in image space for non-corrected PET (PETNC) using deep convolutional neural networks (DCNNs). This approach is a one-step process, distinct from conventional methods that rely on generating attenuation maps first that are then applied to iterative scatter simulation in sinogram space. For training and validation, time-of-flight PET/MR scans and additional helical CTs were performed for 35 subjects (25/10 split for training and test dataset). A DCNN model was proposed and trained to convert PETNC to DCNN-based ASC PET (PETDCNN) directly in image space. For quantitative evaluation, uptake differences between PETDCNN and reference CT-based ASC PET (PETCT-ASC) were computed for 116 automated anatomical labels (AALs) across 10 test subjects (1160 regions in total). MR-based ASC PET (PETMR-ASC), a current clinical protocol in PET/MR imaging, was another reference for comparison. Statistical significance was assessed using a paired t test. The performance of PETDCNN was comparable to that of PETMR-ASC, in comparison to reference PETCT-ASC. The mean SUV differences (mean ± SD) from PETCT-ASC were 4.0% ± 15.4% (P < 0.001) and −4.2% ± 4.3% (P < 0.001) for PETDCNN and PETMR-ASC, respectively. The overall larger variation of PETDCNN (15.4%) was prone to the subject with the highest mean difference (48.5% ± 10.4%). The mean difference of PETDCNN excluding the subject was substantially improved to −0.8% ± 5.2% (P < 0.001), which was lower than that of PETMR-ASC (−5.07% ± 3.60%, P < 0.001). In conclusion, we demonstrated the feasibility of directly producing PET images corrected for attenuation and scatter using a DCNN (PETDCNN) from PETNC in image space without requiring conventional attenuation map generation and time-consuming scatter correction. Additionally, our DCNN-based method provides a possible alternative to MR-ASC for simultaneous PET/MRI.

Predictors of metabolic response in propensity-matched lymphoma patients on interim 18F-fluorodeoxyglucose positron-emission tomography/computed tomography using standardized imaging and reporting protocol: Do we really have one?

The purpose of this prospective study was to determine metabolic response predictor(s) in propensity-matched patients having lymphomas who had baseline and interim 18fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) using strict standardized imaging and reporting protocols. This prospective study was conducted at PET/CT section of a JCI-accredited healthcare facility from April 2017 to February 2018. Patients with baseline and interim 18FDG PET/CT scans using standardized protocol were selected. Interim scans were performed not earlier than 2nd or later than 4th chemotherapy. During the study period, 97 of 112 consecutive patients with lymphomas (Hodgkin-HL: 32/97 and Non-Hodgkin-NHL: 65/97) were included in the study. Mean age of cohort was 45 ± 19 years (71% male and 29% female) having a mean body mass index (BMI) of 25.57 ± 5.54 Kg/m2 having Stage I (21%), Stage II (18%), Stage III (16%), and Stage IV (45%) disease. Bulky disease was found in 14% and 18FDG-avid marrow deposits in 33%. Standardized PET/CT imaging protocol as per EANM guidelines was strictly adopted for baseline and interim studies. %Δ changes in fasting blood sugar, 18FDG dose, uptake time, and liver SUV mean were 3.96%, 2.83%, 2.49%, and 12.15%, respectively. Based on Deauville's scoring, cohort was divided into responders having Score 1–3 (49/97) and nonresponders having Score 4–5 (48/97). The demographic analysis found no significant difference between responders and nonresponders for age, gender, BMI, staging, bulky disease or marrow involvement, and study protocol. No significant coefficient or odd ratios were found on multivariate analysis for age, gender, maximum standardized uptake value (SUVmax), size, BMI, NHL, and advance disease (Stage III and IV) in both groups (χ2: 5.12; receiver operating characteristic [95% confidence interval]: 0.616 [0.51–0.713]; P =0.528). Among responders, baseline SUVmax and tumor size had a direct correlation with a metabolic response on iPET, more pronounced in NHL than HL groups (SUVmax: 13.4 vs. 19.5 and size: 52 vs. 87 mm; P < 0.0001). We conclude that no significant predictor was found for response in propensity-matched patients with lymphomas (both HL and NHL) who had baseline and interim PET/CTs acquired with a standardized protocol. However, NHL responders were found to have higher baseline median SUVmax and larger lesion size as compared to HL responders. Although, these data are not in concordance with published findings but need to be validated with larger studies using standardized imaging and reporting protocols in propensity-matched patients with lymphomas.

FDG PET/CT for metastatic squamous cell carcinoma of unknown primary of the head and neck

ObjectiveThe role of FDG PET/CT is uncertain in squamous cell carcinoma of unknown primary (SCCUP). Published data are limited by heterogeneity of pathology, varied diagnostic criteria, and small sample size. Materials/methodsThis retrospective study was conducted in 40 patients who had FDG PET/CT for SCCUP. Prior to PET/CT, patients had underwent standard clinical evaluations including flexible rhinolaryngoscopy. The majority of the patients had anatomic imaging. All subjects had histopathological investigations, and follow-up data after PET/CT. ResultsFDG PET/CT detected the primary in 16 of 40 patients (40%), and the most common locations of the primary were in the base of the tongue, palatine tonsil, and hypopharynx. There were 10 false positive and 6 false negative PET/CT scans. There was no difference in the mean SUVs of the suspected primary lesions between true and false positive groups. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of FDG PET/CT for SCCUP in this patient cohort were 72.7% (16/22), 44.4% (8/18), 61.5% (16/26), 57.1% (8/14), and 60% (24/40), respectively. The tonsil was the site with the most false positive and false negative findings. ConclusionsFDG PET/CT might be an effective single shot of whole-body imaging for detection of the primary in SCCUP. Low specificity remained the most notable weakness of FDG-PET in work-up for SCCUP. In addition to varied physiologic uptake or inflammatory related uptake in the common locations of the primary, the image indication bias might be another significant contributor of high false positive rate.

Muscle fluorodeoxyglucose uptake assessed by positron emission tomography-computed tomography as a biomarker of inflammatory myopathies disease activity.

To devise a simple PET-CT score for measurement of muscle disease activity in patients with inflammatory myopathies (IMs) and to assess its validity. A total of 44 PET-CT examinations in 34 IM patients (performed during cancer screening) and 20 PET-CT examinations in matched controls (investigated for pulmonary nodules with a conclusion of benignity) were analysed. Maximal standardized uptake values (SUVmax) were recorded bilaterally in eight proximal muscles. The muscle SUVmax (mSUVmax) was defined as the average of the 16 muscle SUVmax values, normalized on the liver mean SUV. Reliability, validity and responsiveness were evaluated. The mSUVmax was increased in IM patients compared with controls. This index allowed the identification of patients with high vs low muscle disease activity using the myositis intention to treat activity index as the gold standard. In patients with subsequent examinations, our method showed good accuracy to detect changes in muscle disease activity [area under the curve 0.96 (95% CI 0.84, 1)]. Responsiveness was strong. Interrater reliability was excellent. PET-CT, a non-invasive tool useful for cancer screening, is also valuable to measure muscle disease activity and its evolution in IM patients.

Association between age, uptake of 18F-fluorodeoxyglucose and of 18F-sodium fluoride, as cardiovascular risk factors in the abdominal aorta.

We aimed to assess the feasibility of quantifying fluorine-18-fluorodexoglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) uptake in abdominal aorta and examine their association with age and cardiovascular risk factors. Our study comprised 123 subjects (48±14 years of age, 62 men) including 78 healthy volunteers and 45 patients with chest pain syndrome, who originally enrolled in the CAMONA study in Odense, Denmark (NCT01724749). All subjects underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and 18F-NaF PET/CT on separate days, 180min and 90min after administration of tracers, respectively. The global tracer uptake value (GTUV) in the abdominal aorta was determined as sum of the product of each slice area and its corresponding average standardized uptake value (SUV mean), divided by the sum of those slice areas. In addition, for each subject, the 10 years Framingham risk score (FRS) was calculated. The correlations between 18F-NaF and 18F-FDG GTUV with age and 10 years FRS were assessed in all, healthy and patient subjects. There was a significant, positive correlation between subjects' age and 18F-NaF GTUV (r=0.35, P<0.001), but not 18F-FDG GTUV (r=0.06, P=0.53). Also, there was a significant, positive correlation between 10 years FRS and 18F-NaF GTUV (r=0.30, P<0.001), but not 18F-FDG GTUV (r=0.01, P=0.95). Individual differences in 18F-FDG and 118F-NaF uptake were large in both healthy subjects and patients. In this study, the global uptake of 18F-NaF in abdominal aorta was positively associated with age and 10 years FRS in all subjects, healthy and patient groups, whereas the global uptake of 18F-FDG was not.

Dosimetry Prediction of 225Ac-NOTA-Trastuzumab Based on 64Cu-NOTA-Trastuzumab in Breast Cancer: Preliminary Microdose Clinical Trial

To predict the internal dosimetry of 225Ac-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-trastuzumab and 225Ac-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab in breast cancer using 64Cu-NOTA-trastuzumab, a novel PET tracer for the HER2 and 64Cu-DOTA-trastuzumab. Prior to injecting the radiotracer, 45 mg of cold trastuzumab was administered for 15 mins. Five patients with breast cancer were injected with 296 MBq of 64Cu-NOTAtrastuzumab. Six patients with breast cancer were injected with 370 MBq of 64Cu-DOTAtrastuzumab. PET/CT was performed 24 and 48 hours after injection. The mean standardized uptake (SUVmean) was evaluated from the blood, liver, kidney, muscle, spleen, bladder, lung, and bone. Furthermore, the radiation activity of 64Cu-NOTA-trastuzumab and 64Cu-DOTA-trastuzumab for each organ was evaluated at imaging time points and the residence time of radiotracer was calculated from the activity of each organ. The internal dosimetry for 64Cu-NOTA-trastuzumab and 64Cu-DOTA-trastuzumab was evaluated using OLINDA/EXM software with an adult female model, which was used for evaluating the internal dosimetry for 225Ac-NOTA-trastuzumab and 225Ac-DOTA-trastuzumab. The overall values of SUVmean in each organ decreased with time on both 64CuNOTA-trastuzumab and 64Cu-DOTA-trastuzumab PET images. However, the bladder showed an increasing pattern of SUVmean over time. In the liver, 64Cu-NOTA-trastuzumab showed relatively lower SUV mean (24 hours; 4.64 ± 0.28, 48 hours; 4.26 ± 0.50) compared to 64Cu-DOTA-trastuzumab (24 hours; 6.66 ± 1.57, 48 hours; 7.05 ± 1.72). 64Cu-DOTAtrastuzumab showed an increasing pattern of the SUVmean in the liver over time. In the blood pool, 64Cu-NOTA-trastuzumab showed relatively higher SUV mean (24 hours; 9.32 ± 1.23, 48 hours; 7.42 ± 1.85) compared to that of 64Cu-DOTA-trastuzumab (24 hours; 7.85 ± 1.76, 48 hours; 6.25 ± 1.64). Other tissues showed similar SUVmean values on both PET images. Any adverse was not reported. The calculated effective doses for 64Cu-NOTA-trastuzumab and 64Cu-DOTA-trastuzumab were 14.3 uSv/MBq and 53.1 uSv/MBq, respectively. 64Cu-NOTA-trastuzumab showed relatively lower radiation burden (46.4 uSv/MBq) compared to that of 64Cu-DOTA-trastuzumab (254 uSv/MBq). The predicted effective doses for 225Ac-NOTA-trastuzumab and 225Ac-DOTA-trastuzumab were 2.19 mSv/MBq and 7.83 mSv/MBq, respectively. In the case of the liver, 225Ac-NOTA-trastuzumab showed lower absorbed dose (8.44 mSv/MBq) compared to that of 225Ac-DOTA-trastuzumab (47.0 mSv/MBq). In the normal liver, lower uptake of 64Cu-NOTA-trastuzumab was observed compared to 64Cu-DOTA-trastuzumab. It may be more helpful to detect metastatic lesions in the liver. Furthermore, when the 64Cu is replaced with 225Ac for treatment purpose, liver damage may be reduced when using NOTA-trastuzumab compared to when using DOTA-trastuzumab.

Correlation between EGFR mutation status and F18 -fluorodeoxyglucose positron emission tomography-computed tomography image features in lung adenocarcinoma.

BackgroundThe purpose of this study was to investigate an association between EGFR mutation status and 18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG PET‐CT) image features in lung adenocarcinoma.MethodsRetrospective analysis of the data of 139 patients with lung adenocarcinoma confirmed by surgical pathology who underwent preoperative 18F‐FDG PET‐CT was conducted. Correlations between EGFR mutation status, clinical characteristics, and PET‐CT parameters, including the maximum standardized uptake value (SUVmax), the mean of the SUV (SUVmean), the peak of the SUV (SUVpeak) of the primary tumor, and the ratio of SUVmax between the primary tumor and the mediastinal blood pool (SUVratio), were statistically analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutation. Receiver operating characteristic curves of statistical quantitative parameters were compared.Results EGFR mutations were detected in 74 (53.2%) of the 139 lung adenocarcinomas and were more frequent in non‐smoking patients. Univariate analysis showed that the SUVmax, SUVmean, SUVpeak, and SUVratio were lower in EGFR‐mutated than in wild‐type tumors. The receiver operating characteristic curves showed no significant differences between their diagnostic efficiencies. Multivariate logistic regression analysis showed that being a never smoker was an independent predictor of EGFR mutation.ConclusionQuantitative parameters based on 18F‐FDG PET‐CT have modest power to predict the presence of EGFR mutation in lung adenocarcinoma; however, when compared to smoking history, they are not good or significant predictive factors.

Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients?

To evaluate the prognostic value of FDG PET/CT metabolic parameter compared to clinico-pathological risk factors in surgical margin-negative stage IA non-small cell lung cancer (NSCLC) patients. 167 patients with consecutive FDG PET/CT scans from 2009 to 2015 performed for staging of NSCLC stage IA with plans for curative surgery were retrospectively reviewed. Maximum standardized uptake value (SUVmax) of primary tumor and mean SUV of liver were acquired from PET/CT. Tumor-to-liver SUV ratio (TLR) was calculated. Charts were reviewed to obtain basic patient characteristics (age, sex, smoking history, LDH, histologic subtype) and high-risk factors for adjuvant chemotherapy (tumor size, poorly differentiation, vascular invasion, and sub-lobar resection). Patients were dichotomized into two groups using optimal cut-off from receiver operating characteristic curve analysis of TLR to predict recurrence. Statistical analysis was done using Cox regression analysis and Kaplan-Meier method. Factors with P < 0.2 in univariate analysis were included in multivariate analysis. Recurrence rate was 12.6% (21/167). Median disease-free survival (DFS) was 47.2months while 2-year and 5-year DFS rates were 93% and 86%, respectively. The optimal cut-off for TLR was 2.3. In univariate analysis, P value of sex, vascular invasion, and TLR were less than 0.2. In multivariable analysis, high TLR was the only factor that showed significant association with tumor recurrence (hazard ratio 3.795, P = 0.0048). TLR was an independent prognostic factor for recurrence and TLR could be an important risk factor to be considered in decision-making for adjuvant chemotherapy, even for those with stage IA NSCLC.

Abstract WP72: Recurrent Cerebral Ischemic Events in Symptomatic Carotid Stenosis are Related to Plaque Inflammation

Background and Aims: Severity of symptomatic carotid stenosis often determines the treatment approach. However, severity explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Inflammation is considered as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high-resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging in stroke recurrence in our patients with recently symptomatic carotid stenosis. Methods: This prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed-up for stroke recurrence within 90-days. Results: Of the 115 patients included in the study, 17 (15%) suffered from recurrent cerebral ischemic event in the stenosed carotid territory within 90-days. Compared to patients who remained asymptomatic, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.19 versus 1.38; p&lt;0.0001) and higher mean SUV value in the carotid plaque (3.04g/ml versus 1.25g/ml; p&lt;0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.215, 95%CI 1.304-5.927; p&lt;0.0001) and higher mean SUV on FDG-PET (OR 3.601, 95%CI 2.924-7.628; p=0.005) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI of carotid stenosis are useful tools for risk stratification and may aid in better therapeutic decision-making.

Significación pronóstica del volumen metabólico tumoral y de la glucólisis tumoral total en pacientes con cáncer cervical avanzado

Aim18-Fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET/CT) is considered to be the most accurate image method of detection of node or distant metastases in cervical cancer. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT are volumetric measurements of tumor cells with increased 18F-FDG uptake. The prognostic value of MTV and TLG in patients with advanced cervical cancer (ACC) were evaluated. Methods38 patients with ACC from one tertiary university hospital underwent 18F-FDG PET/CT between June 2009 and December 2015.Clinicopathologic factors and various PET parameters were analyzed to evaluate their relationship with recurrence-free survival (RFS) and overall survival (OS). These parameters were: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, of the pelvic nodes, of the paraaortic nodes and the metabolic volume of the metastases if any. ResultsA total of 38 patients with ACC fulfilled the inclusion criteria. All of them underwent a 18F-FDG PET/CT before definitive chemoradiotherapy. In the univariate analyses higher tumor size, pelvic lymph node metastasis and both MTV and TLG showed a significant association with OS and with RFS (MTV HR=1.55, p=0.011 and TLG HR=1.43, p=0.017 for RFS and MTV HR=1.82, p=0.006 and TLG HR=1.67, p=0.007 for OS). ConclusionPretreatment TLG sum and MTV sum seem to be independent prognostic factors for OS and RFS in patients with advanced cervical cancer treated with definitive chemoradiotherapy and they are better than the classic measurement of SUVmax.

Can we differentiate malignant peripheral nerve sheath tumor from benign neurofibroma without invasive sampling

One of the most important benign tumors in neurofibromatosis type 1 (NF1) is plexiform neurofibroma, and there is a risk of developing malignant peripheral nerve sheath tumor (MPNST) throughout life approximately 10%. However lesion characterization by anatomical imaging methods are not possible. Because of that most of cases goes to biopsy. Using of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) for lesion characterization can be helpful in NF1 patients. We aimed to present an example of the efficacy of FDG-PET/CT in distinguishing benign neurofibroma from MPNST. A 6-year-old male patient who had NF1 admitted to emergency service due to high fever. Acute upper respiratory tract infection was diagnosed; antipyretic and abundant fluid intake was suggested. When high fever continued, the patient referred to our hospital on detection of axillary lymphadenopathy. Leukocytosis was detected in patient's blood count. Sedimentation was 54 mm/h, C-reactive protein 166 g/L, and lactate dehydrogenase 276U/L. Blood and throat cultures did not show pathogenic bacteria. In serological tests, VZV-IgG, EBV-VCA-IgG, and CMV-IgG were avidite positive; Hepatitis B Ag, Anti-HIV, Anti-HAV IgG and IgM, Anti-HCV, EBV-VCA IgM, and VZV-IgM were negative. Based on these results, cervical and thoracic contrast-enhanced computed tomography was performed on preliminary diagnosis of MPNST. Solid lesions with rounded margins, large one being 49 mm in size, that extend from superior mediastinum to posterior mediastinum, left axillary region, and left part of neck were detected, and they were surrounding the vascular structures. Since neurofibroma, MPNST, and lymphoma could not be distinguished, patient referred to FDG-PET/CT scanning. In FDG-PET/CT, highest lesion maximum standardized uptake value (SUVmax) was 1.5; SUVmax lesion/SUVmax liver 1.0, and SUVmax/ SUV mean liver 1.5. Biopsy from mediastinal and axillary region did not have LN structure and was positive for S-100 immunostaining, and patient was diagnosed as benign neurofibroma. We believe that there is no need for biopsy in lesions considered benign based on FDG-PET/CT parameters.

18F-choline PET/CT incidental thyroid uptake in patients studied for prostate cancer.

Thyroid incidental uptake is defined as a thyroid uptake incidentally detected by imaging examinations performed for non-thyroid disease. The aim of this study was to establish the prevalence and the pathological nature of focal thyroid incidental uptake (FTIU) among patients studied with 18F-choline-PET/CT. We retrospectively evaluated 368 patients who performed 18F-choline-PET/CT between June 2016 and August 2018. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) and the mean SUV (SUVmean) of the thyroid gland and of the FTIU; every focal thyroid uptake deviating from physiological distribution and background was considered FTIU. Final diagnosis of FTIU was obtained by cytological or histological examination after surgery. The average SUVmax and SUVmean of thyroid gland in population were 3 and 1.8. Among 368 patients, FTIU was identified in nine cases (2.4%) and eight underwent further investigations to determine the nature. Two FTIU were classified as malignant (thyroid carcinoma), whereas five were benign (three nodular hyperplasia, one follicular adenoma, one Hurtle cell adenoma) and one indeterminate at cytological examination. In malignant lesions, average SUVmax was 9.6 and 4.5, respectively, while average SUVmean was 5.3 and 2.9, respectively. Average SUVmax and SUVmean of benign lesions were 4.9 and 3.2 and of the indeterminate lesion 5 and 3, respectively. 18F-choline-PET/CT FTIU may be a relevant diagnostic reality, which requires further investigations and affects management, especially considering that, despite being mainly benign, also malignancy is possible.