Absolute Standardized Uptake Value Research Articles

Defining the optimal segmentation method for measuring somatostatin receptor expressing tumor volume on 68Ga-DOTATATE positron emission tomography/computed tomography to predict prognosis in patients with gastroenteropancreatic neuroendocrine tumors.

We aimed to compare different segmentation methods used to calculate prognostically valuable volumetric parameters, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), measured by 68Ga-DOTATATE PET/CT and to find the optimal segmentation method to predict prognosis. Images of 34 patients diagnosed with gastroenteropancreatic neuroendocrine tumor (GEPNET) who underwent 68Ga-DOTATATE PET/CT imaging were reanalyzed. Four different threshold-based methods (fixed relative threshold method, normal liver background threshold method, fixed absolute standardized uptake value (SUV) threshold method, and adaptive threshold method) were used to calculate SRETV and TLSRE values. SRETV of all lesions of a patient was summarized as whole body SRETV (WB-SRETV) and TLSRE of all lesions of a patient was computed as whole body TLSRE (WB-TLSRE). WB-SRETVs calculated with all segmentation methods were statistically significantly associated with progression-free survival except WB-SRETVat which was calculated using adaptive threshold method. The fixed relative threshold methods calculated by using 45% (WB-SRETV45%) and 60% (WB-SRETV60%) of the SUV value as threshold respectively, were found to have statistically significant highest prognostic value (C-index = 0.704, CI = 0.622-0.786, P = 0.007). Among WB-TLSRE parameters, WB-TLSRE35%, WB-TLSRE40%, and WB-TLSRE50% had the highest prognostic value (C-index = 0.689, CI = 0.604-0.774, P = 0.008). The fixed relative threshold method was found to be the most effective and easily applicable method to measure SRETV on pretreatment 68Ga-DOTATATE PET/CT to predict prognosis in GEPNET patients. WB-SRETV45% (cutoff value of 11.8 cm3) and WB-SRETV60% (cutoff value of 6.3 cm3) were found to be the strongest predictors of prognosis in GEPNET patients.

Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and PFS was evaluated using Cox regression. 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) (mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (p < 0.0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant, however it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

Artificial intelligence-based, volumetric assessment of the bone marrow metabolic activity in [18F]FDG PET/CT predicts survival in multiple myeloma.

Multiple myeloma (MM) is a highly heterogeneous disease with wide variations in patient outcome. [18F]FDG PET/CT can provide prognostic information in MM, but it is hampered by issues regarding standardization of scan interpretation. Our group has recently demonstrated the feasibility of automated, volumetric assessment of bone marrow (BM) metabolic activity on PET/CT using a novel artificial intelligence (AI)-based tool. Accordingly, the aim of the current study is to investigate the prognostic role of whole-body calculations of BM metabolism in patients with newly diagnosed MM using this AI tool. Forty-four, previously untreated MM patients underwent whole-body [18F]FDG PET/CT. Automated PET/CT image segmentation and volumetric quantification of BM metabolism were based on an initial CT-based segmentation of the skeleton, its transfer to the standardized uptake value (SUV) PET images, subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, ten different uptake thresholds (AI approaches), based on reference organs or absolute SUV values, were applied for definition of pathological tracer uptake and subsequent calculation of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Correlation analysis was performed between the automated PET values and histopathological results of the BM as well as patients' progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curve analysis was used to investigate the discrimination performance of MTV and TLG for prediction of 2-year PFS. The prognostic performance of the new Italian Myeloma criteria for PET Use (IMPeTUs) was also investigated. Median follow-up [95% CI] of the patient cohort was 110months [105-123months]. AI-based BM segmentation and calculation of MTV and TLG were feasible in all patients. A significant, positive, moderate correlation was observed between the automated quantitative whole-body PET/CT parameters, MTV and TLG, and BM plasma cell infiltration for all ten [18F]FDG uptake thresholds. With regard to PFS, univariable analysis for both MTV and TLG predicted patient outcome reasonably well for all AI approaches. Adjusting for cytogenetic abnormalities and BM plasma cell infiltration rate, multivariable analysis also showed prognostic significance for high MTV, which defined pathological [18F]FDG uptake in the BM via the liver. In terms of OS, univariable and multivariable analysis showed that whole-body MTV, again mainly using liver uptake as reference, was significantly associated with shorter survival. In line with these findings, ROC curve analysis showed that MTV and TLG, assessed using liver-based cut-offs, could predict 2-year PFS rates. The application of IMPeTUs showed that the number of focal hypermetabolic BM lesions and extramedullary disease had an adverse effect on PFS. The AI-based, whole-body calculations of BM metabolism via the parameters MTV and TLG not only correlate with the degree of BM plasma cell infiltration, but also predict patient survival in MM. In particular, the parameter MTV, using the liver uptake as reference for BM segmentation, provides solid prognostic information for disease progression. In addition to highlighting the prognostic significance of automated, global volumetric estimation of metabolic tumor burden, these data open up new perspectives towards solving the complex problem of interpreting PET scans in MM with a simple, fast, and robust method that is not affected by operator-dependent interventions.

A Prognostic Model Integrating Circulating Clonal Plasma Cells into R-ISS and PET-CT Based Tumor Burden in Transplant-Ineligible Multiple Myeloma

Introduction: Circulating clonal plasma cell (cCPC) is an easily obtained and non-invasive biomarker in multiple myeloma (MM), providing distinct prognostic information from the revised-international staging system (R-ISS). However, its prognostic relevance has been investigated primarily in transplant-eligible and clinical trial settings. Consequently, there is limited data on the impact of cCPC on outcomes and optimal cut-off values in transplant-ineligible (TIE) MM patients. Moreover, appropriate combinations to refine risk stratification, such as tumor burden measured by positron emission tomography-computed tomography (PET-CT), have yet to be fully explored. Methods: We performed a retrospective analysis on newly diagnosed TIE-MM patients with available peripheral blood (PB) flow cytometry (FCM) and PET-CT data from 2011 to 2021. Patients with primary plasma cell leukemia (n=8), defined as &amp;gt;5% monoclonal plasma cells in PB, were excluded from the study. Quantification of cCPC was performed using 6-color (2011-2016) or 8-color (2017-2021) FCM staining for CD19, CD56, CD38, CD138, cytoplasmic κ, and cytoplasmic λ to confirm monoclonality (Beckman Coulter, USA), which required at least 150000 mononuclear cell counts with the detectable limit at 0.01% (10 -4) based on previous reports (Gonsalves et al). Tumor burden was assessed by calculating total lesion glycolysis (TLG) using the following formula: the mean standardized uptake value (SUV) multiplied by the total tumor volume with an absolute SUV &amp;gt;2.5, using Metavol Software (Hokkaido University, Japan). Receiver operating curve analysis with the Youden index was employed to determine the optimal cutoff for predicting 2-year progression-free survival (PFS) and 5-year overall survival (OS). The predictive performance of R-ISS, cCPC, and TLG alone, along with their combinations, was compared using Harrell's concordance index (c-index). Results: 114 patients with TIE-MM were analyzed. The median age was 78 years (interquartile range [IQR] 73-83). The number of patients classified as R-ISS Ⅰ, Ⅱ, and Ⅲ was 12 (10.5%), 82 (71.9%), and 20 (17.5%), respectively. Most patients (85.1%) received proteasome inhibitor-based induction remission therapy. cCPCs were detectable in 90 patients (80.7%), with a median level of 6 ×10 -4 (IQR 1-22). Regarding tumor burden, 73 patients (64%) had at least one fluorodeoxyglucose avid lesion with a median TLG of 34.7 (IQR 0-268). cCPC levels were significantly correlated with CPC in bone marrow (R =0.24, P =0.01) but not with TLG (R =-0.01, P =0.88) and involved free light chain levels (R =0.07, P =0.41). The optimal cut-off values in predicting 2-year PFS and 5-year OS were 9 and 10 ×10 -4 for cCPC, and 325 and 343 for TLG, respectively. For simplicity, we classified &amp;gt;10 ×10 -4 for cCPC and &amp;gt;300 for TLG as high-risks. Notably, approximately two-thirds of the patients (62.3%) had at least one high-risk feature (Figure 1). Both high cCPC and TLG showed significant associations with worse OS and PFS (5-year OS rate: cCPC high vs. low, 40.2% vs. 69.3%; TLG high vs. low, 38% vs. 64.5%; 2-year PFS rate: cCPC high vs. low, 45.7% vs. 69.1%; TLG high vs. low, 46.4% vs. 64% all P &amp;lt; 0.05). These factors retained prognostic significance after adjustment for R-ISS on multivariate analysis. Finally, we constructed a novel predictive model integrating RISS, cCPC, and TLG. This model discriminated OS among patients with 0 (5-year OS rate, 80% [95% confidence interval 68.4%-93.6%]), 1 (50.5% [37.7%-67.7%]), and ≧2 factors (29% [13.3%-63.5%], P &amp;lt;0.001, Figure 2). The c-index was the highest (0.651) in this combined model compared to the single use of these risk factors (0.585, 0.594, and 0.569). Conclusions: We demonstrated the prognostic impact of cCPC, which is independently associated with R-ISS and TLG, on real-world TIE-MM patients. The new prediction model, integrated with these different clinical and biological features, may provide robust outcome discrimination.

Early Post-ischemic Brain Glucose Metabolism Is Dependent on Function of TLR2: a Study Using [18F]F-FDG PET-CT in a Mouse Model of Cardiac Arrest and Cardiopulmonary Resuscitation

PurposeThe mammalian brain glucose metabolism is tightly and sensitively regulated. An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a crucial role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study, glucose metabolism was measured using non-invasive [18F]F-FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild-type (WT) and TLR2-deficient (TLR2−/−) mice. The investigation will evaluate whether FDG-PET could be useful as an additional methodology in assessing prognosis.ProceduresTwo PET-CT scans using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) tracer were carried out to measure dynamic glucose metabolism before and early after CPR. To achieve this, anesthetized and ventilated adult female WT and TLR2−/− mice were scanned in PET-CT. After recovery from the baseline scan, the same animals underwent 10-min KCL-induced CA followed by CPR. Approximately 90 min after CA, measurements of [18F]F-FDG uptake for 60 min were started. The [18F]F-FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas.ResultsThe absolute SUVmean of glucose in the whole brain of WT mice was increased about 25.6% after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2−/− mice was not significantly different between baseline and measurements post CA-CPR. In comparison, baseline measurements of both mouse strains show a highly significant difference with regard to the absolute glucose SUV in the whole brain. Values of TLR2−/− mice revealed a 34.6% higher glucose uptake.ConclusionsThe altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions, whereby the post-ischemic differences in glucose metabolism were associated with the function of key immune factor TLR2. There is evidence for using early FDG-PET-CT as an additional diagnostic tool after resuscitation. Further studies are needed to use PET-CT in predicting neurological outcomes.

DeepTOFSino: A deep learning model for synthesizing full-dose time-of-flight bin sinograms from their corresponding low-dose sinograms

PurposeReducing the injected activity and/or the scanning time is a desirable goal to minimize radiation exposure and maximize patients’ comfort. To achieve this goal, we developed a deep neural network (DNN) model for synthesizing full-dose (FD) time-of-flight (TOF) bin sinograms from their corresponding fast/low-dose (LD) TOF bin sinograms. MethodsClinical brain PET/CT raw data of 140 normal and abnormal patients were employed to create LD and FD TOF bin sinograms. The LD TOF sinograms were created through 5% undersampling of FD list-mode PET data. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). Residual network (ResNet) algorithms were trained separately to generate FD bins from LD bins. An extra ResNet model was trained to synthesize FD images from LD images to compare the performance of DNN in sinogram space (SS) vs implementation in image space (IS). Comprehensive quantitative and statistical analysis was performed to assess the performance of the proposed model using established quantitative metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM) region-wise standardized uptake value (SUV) bias and statistical analysis for 83 brain regions. ResultsSSIM and PSNR values of 0.97 ± 0.01, 0.98 ± 0.01 and 33.70 ± 0.32, 39.36 ± 0.21 were obtained for IS and SS, respectively, compared to 0.86 ± 0.02and 31.12 ± 0.22 for reference LD images. The absolute average SUV bias was 0.96 ± 0.95% and 1.40 ± 0.72% for SS and IS implementations, respectively. The joint histogram analysis revealed the lowest mean square error (MSE) and highest correlation (R2 = 0.99, MSE = 0.019) was achieved by SS compared to IS (R2 = 0.97, MSE= 0.028). The Bland & Altman analysis showed that the lowest SUV bias (-0.4%) and minimum variance (95% CI: -2.6%, +1.9%) were achieved by SS images. The voxel-wise t-test analysis revealed the presence of voxels with statistically significantly lower values in LD, IS, and SS images compared to FD images respectively. ConclusionThe results demonstrated that images reconstructed from the predicted TOF FD sinograms using the SS approach led to higher image quality and lower bias compared to images predicted from LD images.

NEIM-05. [GA68]DOTATATE PET/MRI-BASED RADIOSURGICAL RESPONSE ASESSMENT IN MENINGIOMA

Abstract PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas. METHODS Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests. RESULTS 13 patients (15% WHO-I, 54% WHO-II, 23% WHO-III, 8% WHO grade unknown) were followed postoperatively with pre- and post-RT DOTATATE PET/MRI. 29 meningiomas were treated. 46% (6/13) of subjects received SBRT and 54% (7/13) received SRS. Post-RT DOTATATE PET/MRI demonstrated a 46.4% SUV decrease (p-value = 0.0001) and a 60.8% SUVR decrease (p-value &amp;lt; 0.0001). Of 21 measurable lesions, the size product decreased by 21%; while this decrease was statistically significant (p-value = 0.0008), it was below the 25% decrease defined as clinically significant by RANO guidelines. To date, all patients remain stable radiographically without evidence of recurrence (mean follow-up post RT: 14 months; range: 6-24 months). CONCLUSIONS DOTATATE PET SUV and SUVR demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant but not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising approach to aid in response assessment for radiosurgically treated meningiomas. Longer-term follow-up is needed to determine the correlation between the degree of post-RT SUV and/or SUVR decrease and progression-free-survival.

Optimal Standardized Uptake Value Threshold for Auto contouring of Gross Tumor Volume using Positron Emission Tomography/Computed Tomography in Patients with Operable Nonsmall-Cell Lung Cancer: Comparison with Pathological Tumor Size.

Purpose:Incorporating 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) for gross tumor volume (GTV) delineation is challenging due to varying tumor edge based on the set threshold of the standardized uptake value (SUV). This study aims to determine an optimal SUV threshold that correlates best with the pathological tumor size.Materials and Methods:From January 2013 to July 2014, 25 consecutive patients of operable nonsmall-cell lung cancer (NSCLC) who underwent staging18F-FDG-PET/CT before surgical resection were included in the test cohort and 12 patients in the validation cohort. GTVs were delineated on the staging PET/CT by automatic delineation using various percentage threshold of maximum SUV (SUVmax) and absolute SUV. The maximum pathological tumor diameter was then matched with the maximum auto-delineated tumor diameter with varying SUV thresholds. First-order linear regression and Bland–Altman plots were used to obtain an optimal SUV threshold for each patient. Three radiation oncologists with varying degrees of experiences also delineated GTVs with the visual aid of PET/CT to assess interobserver variation in delineation.Results:In the test set, the mean optimal percentage threshold for GTV was SUVmax of 35.6%±18.6% and absolute SUV of 4.35 ± 1.7. In the validation set, the mean optimal percentage threshold SUV and absolute SUV were 36.9 ± 16.9 and 4.1 ± 1.6, respectively. After a combined analysis of all 37 patients, the mean optimal threshold was 36% ± 17.9% and 4.27 ± 1.7, respectively. Using Bland–Altman plots, auto-contouring with 40% SUVmax and SUV 4 was in greater agreement with the pathological tumor diameter.Conclusion:Automatic GTV delineation on PETCT in NSCLC with percentage threshold SUV of 40% and absolute SUV of 4 correlated best with pathological tumor size. Auto-contouring using these thresholds will increase the precision of radiotherapy contouring of GTV and will save time.

Accuracy of metabolic volume and total glycolysis among six threshold-based target segmentation algorithms.

This study aimed to evaluate the accuracy of six threshold-based segmentation methods with different target-to-background ratios (TBR), images with different voxel sizes and image noise, in measuring metabolic volume (MV) and total glycolysis (TG). A standard body phantom consisting of six spheres (inner diameters of 37, 28, 22, 17, 13, and 10mm) was filled with 18F-FDG solution. The background radioactivity level was 2.65kBq/mL, and the TBRs were 4 and 8. PET data were acquired for 30min with list mode. PET data for 30 and 3min were reconstructed with a three-dimensional ordered subset expectation maximization algorithm plus time-of-flight information with images with 2 and 4mm isotropic voxels. The six methods examined were absolute standardized uptake value (SUV) of 2.5 (SUV2.5), 41%, 50%, adaptive 41%, and adaptive 50% thresholds of maximum SUV (Th41, Th50, ThA41, and ThA50, respectively); and the contrast-oriented algorithm (ThCOA). Segmented MV and TG were compared with the actual inner volume and expressed as percentages (%MVseg and %TGseg, respectively). In addition, the segmented MV was converted to the diameter, and the differences of it from the reference diameter were compared among six methods. The ThCOA method yielded the most accurate measurements of %MVseg and %TGseg; the difference between %MVseg or %TGseg and its reference were smaller than 10% in 30-min and 15% in 3-min images, but the segmented contour was almost the same as the reference diameter. Measurements with Th50 and ThCOA were highly accurate for both %MVseg and %TGseg in the large spheres, and the adaptive threshold methods, including ThA41, ThA50, and ThCOA, were also highly accurate in the small spheres. The voxel sizes affected the accuracy of %MVseg and %TGseg with a TBR of 4 in any threshold-based methods. Of the six threshold-based segmentation methods studied, ThCOA was the most accurate method for evaluating MV and TG and had only minor dependence on TBRs and sphere size. The small voxel sizes improved the variation of the accuracy in low TBR.

Optimization of parathyroid 11C-choline PET protocol for localization of parathyroid adenomas in patients with primary hyperparathyroidism

PurposeTo evaluate the optimal tracer uptake time, the minimal amount of radioactivity and the inter-observer agreement for 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with primary hyperparathyroidism (pHPT).MethodsTwenty-one patients with biochemically proven pHPT were retrospectively studied after injection of 6.3 ± 1.2 MBq/kg 11C-choline. PET data of the first nine patients, scanned for up to 60 min, were reconstructed in 10-min frames from 10- to 60-min postinjection (p.i.), mimicking varying 11C-choline uptake times. Parathyroid adenoma to background contrast ratios were calculated and compared, using standardized uptake values (SUVs). Data was reconstructed with varying scan durations (1, 2.5, 5, and 10 min) at 20–30-min p.i. (established optimal uptake time), mimicking less administered radioactivity. To establish the minimal required radioactivity, the SUVs in the shorter scan durations (1, 2.5, and 5 min) were compared to the 10-min scan duration to determine whether increased variability and/or statistical differences were observed. Four observers analyzed the 11C-choline PET/CT in four randomized rounds for all patients.ResultsSUVpeak of the adenoma decreased from 30 to 40 p.i. onwards. All adenoma/background contrast ratios did not differ from 20- to 30-min p.i. onwards. The SUVs of adenoma in the scan duration of 1, 2.5, and 5 min all differed significantly from the same SUV in the 10-min scan duration (all p = 0.012). However, the difference in absolute SUV adenoma values was well below 10% and therefore not considered clinically significant. The inter-observer analysis showed that the Fleiss’ kappa of the 1-min scan were classified as “moderate,” while these values were classified as “good” in the 2.5-, 5-, and 10-min scan duration. Observers scored lower certainty scores in the 1- and 2.5-min scans compared to the 5- and 10-min scan durations.ConclusionThe optimal time to start PET/CT scanning in patients with pHPT is 20 min after mean injection of 6.3 MBq/kg 11C-choline, with a recommended scan duration of at least 5 min. Alternatively, the radioactivity dose can be lowered by 50% while keeping a 10-min scan duration without losing the accuracy of 11C-choline PET/CT interpretation.

Using 18F-FDG PET/CT to Estimate the Length of Gross Tumor and Involvement of Lymph Nodes in Esophagogastric Junction Carcinoma

To determine the optimal method to estimate length of gross tumor and involvement of lymph nodes of using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in esophagogastric junction carcinoma (EGJC) verified by pathologic examination. Twenty patients with newly diagnosed and untreated EGJC were enrolled, with all of them then being treated with radical surgery. Every patient underwent a whole-body 18F-FDG PET/CT imaging within a week before the operation. The length of the gross tumor on PET/CT was measured using different methods: standardized uptake value (SUV) 1.5 – 5.5 in intervals of 1.0, and 10% – 50% of maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT in intervals of 10%, and recorded as L1.0 to L5.0, and L10% to L50%, respectively. Measurements of gross tumor length were made at operation before the esophagogastric junction specimen was removed (in-vivo, Lvivo), and also with the specimen lying free (contracted, Lvitro). The shrinkage ratio for the primary tumor was calculated as Lvitro/Lvivo, and was then used to calculate the pathological length of tumor (Lpath). We observed the measurable lymph nodes on PET/CT preoperative, labeled them during operation, and examined for pathology. The t test and Wilcoxon Signed Ranks Test were used to assess the differences between groups, Spearman correlation and Pearson correlation was performed to assess the relationship between groups. A receiver operating characteristic curve was to determine the cut-off SUVmax for detecting lymph node metastases. Lpath was 6.87 ± 2.25 cm, L30% and L2.5 were 6.61 ± 1.76 cm and 7.56 ± 1.89 cm, respectively. L30% was more approximate to Lpath than the other % SUVmax, L2.5 was more approximate to Lpath than the other absolute SUV. The difference between L30% and L2.5 was not significantly different (p = 0.107). Two hundred eight lymph nodes were included in our study, 158 lymph nodes were negative, and 50 lymph nodes were positive. The 18F-FDG PET/CT had the best diagnostic performance for lymph nodes at the cut-off SUV of 2.7, the sensitivity, specificity, positive predictive value, negative predictive value, false-negative rate (FNR), false-positive rate (FPR), and accuracy of 18F-FDG PET/CT in detecting lymph node metastases were 72%, 83.54%, 58.06%, 90.41%, 28%, 16.46%, and 80.77%. To identify an SUV threshold for the distinction of benign lymph nodes from malignant lymph nodes, we plotted the error rates of positive and negative interpretations against a hypothetical SUV threshold. The minimal FNR+FPR was achieved at an SUV of 2.7. A 30% SUVmax and SUV 2.5 threshold of 18F-FDG PET/CT provided closest estimation of the length of gross tumor in EGJC. The 18F-FDG PET/CT had the best diagnostic efficiency at the cut-off SUVmax of 2.7 for detecting lymph node metastases in EGJC.

The Baseline Pattern and Age-related Developmental Metabolic Changes in the Brain of Children with Autism as Measured on Positron Emission Tomography/Computed Tomography Scan.

[18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan was performed on 45 children with autism to study the baseline pattern and age-related developmental changes in the brain metabolism. Median standardized uptake values (SUVs) were compared with published healthy control data. Results showed that, in contrary to control data, the median SUVs in children with autism decrease linearly with increase in age. As compared to controls, autism children below 5 years showed greater metabolism and older children showed lower metabolism. In autism group, comparison of absolute SUVs within different regions of the brain revealed relatively lower metabolism in amygdala, hippocampus, parahippocampal gyrus, caudate nucleus, cerebellum, mesial temporal lobe, thalamus, superior and middle temporal pole, and higher metabolic uptake in calcarine fissure and Heschl's gyrus. These results help in understanding the baseline metabolism and developmental changes of brain among different age groups in autism.

Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network.

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a range of 11%. Dose calibrator bias was not correlated with scanner bias. Calibration factors from the image metadata were nearly as variable as scanner signal, and were correlated with signal for many scanners. SUVs often showed low intrascanner variability between successive measurements but were also prone to shifts in apparent bias, possibly in part due to scanner recalibrations that are part of regular scanner quality control. Biases of key factors in the computation of SUVs were not correlated and their temporal variations did not cancel out of the computation. Long-lived sources and image metadata may provide a check on the recalibration process.

Using 18F-fluorodeoxyglucose positron emission tomography/computed tomography to estimate the length of gross tumor and involvement of lymph nodes in esophagogastric junction carcinoma.

To determine the optimal approach for estimating the length of gross tumor and involvement of the lymph nodes with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in esophagogastric junction carcinoma (EGJC). The result was verified with pathologic examination. Twenty patients with diagnosed and untreated EGJC were enrolled. The length of the gross tumor was measured using different approaches with PET/CT: Standardized uptake value (SUV) 1.5-5.5 in intervals of 1.0 and 10%-50% of maximum SUV (SUVmax) on 18F-FDG PET/CT in intervals of 10%. The results were expressed as L1.0-L5.0, and L10%-L50%, respectively. The pathological length of gross tumor (Lpath) was calculated based on the shrinkage ratio of primary tumor. The measurable lymph nodes were measured on PET/CT preoperatively, labeled during operation, and examined for pathology. Lpath was 6.87 ± 2.25 cm, L30% and L2.5 were 6.61 ± 1.76 cm and 7.56 ± 1.89 cm, respectively. L30% was closer to Lpath than other % SUVmax, L2.5 was closer to Lpath than other absolute SUV thresholds. The diagnostic performance of 18F-FDG PET/CT for lymph nodes was best at the cutoff SUV of 2.7, providing sensitivity of 70% and a specificity of 83.7% for detecting lymph node metastases. The tumor length with 30% SUVmax as the threshold was closest to the actual pathological length of EGJC. The diagnostic efficiency of 18F-FDG PET/CT was best at the cutoff SUVmax of 2.7 for detecting lymph node metastases in EGJC.

Comparison of Tumor Volumes as Determined by Pathologic Examination and FLT-PET/CT Images of Non–Small Cell Lung Cancer: A Pilot Study

To determine the cut-off standardized uptake value (SUV) on 3-deoxy-3-18F-fluorothymidine (FLT) positron emission tomography/computed tomography (FLT-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTVpath) for non–small cell lung cancer (NSCLC). Twelve patients with NSCLC who, without any antineoplastic therapy before, underwent FLT-PET/CT scans one or two days followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7 μm sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTVpath determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTVPET, was determined as a function of cut-off SUV. Then, the GTV PET(SUV) value was determined at different cut-off values of the absolute SUV, from 0.9 to 1.8 at 0.1 intervals. Similarly, GTVPET(%SUV) was determined at various percentage thresholds of the maximal SUV, from 15% to 60% at 5% intervals. The optimal threshold or optimal absolute SUV was defined as the value at which the GTVPET was the same as the GTVpath. The patients included 5 men and 7 women, with a median age of 62 years (range, 43–71). The pathologic classifications were 8 adenocarcinoma and 4 squamous cell carcinoma. The locations of the tumors were 3 superior lobe of left lung, 2 inferior lobe of left lung, 5 superior lobe of right lung, and 2 inferior lobe of right lung, respectively. The fixation process induced a volumetric reduction to 70.84% ± 5.71% (range, 60.4%-79.7%) of the original tumor volumes. The maximal SUV was 3.50 ± 0.97 (range, 1.96-5.05). The GTVpath was 11.07± 10.30 cm3 (range, 2.39-33.10cm3). The mean optimal threshold and absolute SUV that produced the best agreement between GTVpath and GTVPET were 56% ± 11% and 1.84 ± 0.33, respectively. The optimal absolute SUV had a positive correlation with maximal SUV (P=.037), whereas the optimal threshold had no significant correlation with it (P=.52). On the other hand, the optimal threshold was correlated with volume retraction (P<.05), but the optimal absolute SUV had no significant correlation with volume retraction (P>.05). This study evaluated the use of GTVpath as a criterion for determining the FLT-PET/CT images’ optimal cut-off SUV for NSCLC. Absolute SUV 1.8 and threshold 56% might be used as the optimal cut-off SUV for NSCLC target volume delineation.

An Absolute Standardized Uptake Value Is More Useful than the Decreased Rate of Uptake of FDG-PET to Predict Responses to Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Background: Neoadjuvant chemoradiotherapy (CRT) is frequently performed for esophageal squamous cell carcinoma. In this study, we retrospectively assessed the standardized uptake value (SUV) of FDG-PET against decreased rates of SUV to assess the response of advanced esophageal squamous cell carcinoma patients to neoadjuvant CRT, and the correlation of this response with histopathological findings. Patients and Methods: Thirty-three patients receiving CRT followed by surgery were analyzed. Results: Using the decreased rate of maximum SUV, the sensitivity and specificity in distinguishing complete responders (CR) from non-CR patients was 63% and 44%. Using the maximum SUV before surgery, the sensitivity and specificity for distinguishing pathological CR from non-CR was 88% and 56%. Conclusions: To identify complete responders of CRT for esophageal cancer, absolute maximum SUV value is a better predictor than decreased rate of the maximum SUV.

Value of functional imaging by PET in esophageal cancer.

In esophageal cancer, functional imaging using PET can provide important additional information beyond standard staging techniques that may eventually lead to therapeutic consequences. The most commonly used tracer is fluorodeoxyglucose (FDG), which has high avidity for both squamous cell cancer and adenocarcinoma of the esophagus. The value of FDG-PET is limited in early esophageal cancer, whereas additional information is provided in 15% to 20% of locally advanced tumors. Neoadjuvant treatment is currently the standard of care in locally advanced esophageal cancer in most countries because randomized studies have shown a significant survival benefit. Because responders and nonresponders have a significantly different prognosis, functional imaging to tailor preoperative treatment would be of interest. Metabolic imaging using FDG-PET is an established method of response evaluation in clinical trials. The value of metabolic response evaluation is known to depend on the histologic subtype and the type of preoperative treatment delivered. An association of FDG-PET-based metabolic response with clinical response and prognosis was shown for absolute standardized uptake value (SUV) or a decrease of SUV levels before, during, and after therapy. However, contradictory findings exist in the literature and prospective validation is missing. Additionally, no consensus exists on time points or cutoff levels for metabolic response evaluation. Furthermore, correct prediction of a posttherapeutic pathologic complete remission is currently not possible using FDG-PET. Of high interest is early response monitoring during preoperative chemotherapy, with potential subsequent therapy modification. This tailored approach still needs validation in prospective multicenter trials.

Comparison of Tumor Volumes as Determined by Pathologic Examination and FLT-PET/CT Images of Non-Small Cell Lung Cancer: A Pilot Study

To determine the cut-off standardized uptake value (SUV) on 3-deoxy-3-18F-fluorothymidine (FLT) positron emission tomography/computed tomography (FLT-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTVpath) for non-small-cell lung cancer (NSCLC). Twelve patients with NSCLC who without any antineoplastic therapy before, underwent FLT-PET/CT scans one or two days followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7 μm sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTVpath determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTVPET, was determined as a function of cut-off SUV. Then, the GTV PET(SUV) value was determined at different cut-off values of the absolute SUV, from 1.0 to 2.0 at 0.1 intervals. Similarly, GTVPET(%SUV) was determined at various percentage thresholds of the maximal SUV, from 15% to 60% at 5% interval. The optimal threshold or optimal absolute SUV was defined as the value at which the GTVPET was the same as the GTVpath. The patients included 5 men and 7 women, with a median age of 62 years (range, 43-71). The pathologic classifications were 8 adenocarcinoma and 4 squamous cell carcinoma. The location of the tumors were 3 superior lobe of left lung, 2 inferior lobe of left lung, 5 superior lobe of right lung and 2 inferior lobe of right lung, respectively. The fixation process induced a volumetric reduction to 70.84% ± 5.71% (range, 60.4-79.7%) of the original tumor volumes. The maximal SUV was 3.50 ± 0.97 (range, 1.96-5.05). The GTVpath was 11.07± 10.30 cm3(range, 2.39-33.10cm3). The mean optimal threshold and absolute SUV that produced the best agreement between GTVpath and GTVPET were 56% ± 11% and 1.84 ± 0.33, respectively. The optimal absolute SUV had a positive correlation with maximal SUV (p = 0.037), whereas the optimal threshold had no significant correlation with it (p = 0.52). On the other hand, the optimal threshold was correlated with volume retraction (p<0.05), but the optimal absolute SUV had no significant correlation with volume retraction (p> 0.05). This study evaluated the use of GTVpath as a criterion for determining the FLT-PET/CT images optimal cut-off SUV for NSCLC. Absolute SUV 1.8 and threshold 56% might be used as the optimal cut-off SUV for NSCLC target volume delineation.

Importance of PET in surgery of esophageal cancer

Perioperative or preoperative radiochemotherapy (RCTx) is nowadays standard for locally advanced esophageal cancer in Europe, as randomized studies have shown a significant survival benefit for patients with multimodal treatment. As responders and nonresponders have a significantly different prognosis, a response-based tailored preoperative treatment would be of utmost interest. An established method is a metabolic response evaluation by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The level of metabolic response is known to be dependent on the localization, tumor entity and type of preoperative treatment. Association of FDG-PET with later response and prognosis was shown for absolute standardized uptake values (SUV) or a decrease of SUV levels before and after therapy but there are also contradictory findings in the literature and no prospective validation. However, neither time points nor cut-off for metabolic response evaluation have been defined so far. The most interesting approach seems to be early response monitoring during preoperative chemotherapy, which has shown promising results in prospective single center trials (MUNICON I/II) during chemotherapy of adenocarcinoma of the esophagogastric junction (AEG), but needs to be validated in prospective multicenter trails.

Abstract P4-01-01: Serial FDG and 18F-fluoride PET predict response to therapy in patients with breast cancer bone metastases

Abstract Background: Assessing response to therapy in patients (pts) with bone-dominant (BD) metastatic breast cancer is challenging by conventional imaging such as CT and bone scintigraphy. In prior retrospective analyses, measures of FDG uptake by FDG PET were predictive of both time to progression (TTP) and the risk of skeletal related events (SRE). Studies have also shown that 18F-fluoride PET improves bone metastasis detection compared to bone scintigraphy and, as a quantitative study, may be better suited to evaluate therapeutic response. We evaluated the utility of serial FDG PET and 18F-fluoride PET to prospectively assess response to therapy in BD metastatic breast cancer. Methods: Pts with BD metastatic breast cancer were evaluated with FDG PET and 18F-fluoride PET prior to starting a new systemic therapy and after approximately 3 months. Serum markers (CA27.29 and CEA) were obtained at baseline and during treatment close to the time of PET imaging. In this analysis, static images from skull base to mid-thighs were analyzed quantitatively using the maximum standardized uptake value (SUV) of up to 5 most prominent lesions. Tumor locations were confirmed by CT and regions-of-interest were drawn on both FDG and 18F-fluoride images. Assessment of clinical endpoints including TTP and time to SRE was determined by independent review of clinical data and analyzed by Cox regression. PET imaging results were reported clinically, but not used to determine endpoints in this analysis. Results: 47 pts (mean age 55, range 39-91) enrolled between 2004 and 2012. Most pts 43/47 (91%) had hormone receptor positive disease (primary or metastatic). 9/47 (19%) of pts had HER2+ disease. Systemic therapy during study was chemotherapy in 20/47 (43%) and endocrine therapy in 31/47 (66%). Most pts 30/47 (64%) received bisphosphonates. Mean time between baseline and follow up FDG and 18F-fluoride PET scans was 4.6 months. 42/47 (89%) pts had disease progression during study follow up (median TTP 5.9 months, 95% CI 4-9.2). Among 24 pts with 2 FDG and 2 18F-fluoride scans, percent change in FDG (&amp;gt;-9% vs ≤-9%) was predictive of TTP, HR = 0.317, p = 0.038. Percent change (&amp;gt;-19% vs ≤-19%) in 18F-fluoride SUV did not predict TTP, HR = 1.05, p = 0.914. Median time to SRE was 48 months. Absolute SUV for baseline FDG and 18F-Fluoride PET were both predictive of time to SRE (FDG SUV &amp;gt;6 vs &amp;lt;6; HR = 4.61, p = 0.002 and 18F-fluoride SUV &amp;gt;25 vs &amp;lt;25; HR = 4.5, p = 0.008). Conclusions: Changes in FDG SUV over the course of treatment were a robust predictor of TTP, while changes in 18F-fluoride PET did not predict response. Both baseline high FDG and 18F-fluoride SUV were associated with earlier SRE occurrence. These results indicate a role for PET, particularly FDG PET, in assessing BD breast cancer and support a role for PET in future clinical trials. Funding support 5R01CA124573-05. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-01.