Peak Standardized Uptake Value Research Articles

PET response criteria for solid tumors predict survival at three months after intra-arterial resin-based 90Yttrium radioembolization therapy for unresectable intrahepatic cholangiocarcinoma.

PET Response Criteria for Solid Tumors (PERCIST) were assessed and correlated with survival analysis after resin-based 90Yttrium (90Y) radioembolization therapy for intrahepatic cholangiocarcinoma (ICC). Target and overall PERCIST and Response Criteria for Solid Tumors (RECIST) treatment responses were assessed in consecutive patients treated with Y radioembolization for ICC refractory to standard chemotherapy. Significant measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or greater in targeted and nontargeted lesions. The PERCIST defines complete response as resolution of 18F-FDG uptake within measurable lesions, and partial response as 30% reduction in 18F-FDG peak standardized uptake value in measurable lesions. Objective response included partial response and complete response. Survival analysis by Kaplan-Meier and log-rank proportional models was performed using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P < 0.05. Median overall survival (OS) of 9 consecutive patients (56% women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST objective response rate of target lesions was 77.7%, and target objective response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall objective PERCIST response at 3 months had significant correlation with OS (P = 0.011). Probability of death was significantly higher in overall nonresponders by PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST. In patients with unresectable ICC refractory to standard chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y radioembolization therapy predict OS.

Efficiency gains in tracer identification for nuclear imaging: can in vivo LC-MS/MS evaluation of small molecules screen for successful PET tracers?

Positron emission tomography (PET) imaging has become a useful noninvasive technique to explore molecular biology within living systems; however, the utility of this method is limited by the availability of suitable radiotracers to probe specific targets and disease biology. Methods to identify potential areas of improvement in the ability to predict small molecule performance as tracers prior to radiolabeling would speed the discovery of novel tracers. In this retrospective analysis, we characterized the brain penetration or peak SUV (standardized uptake value), binding potential (BP), and brain exposure kinetics across a series of known, nonradiolabeled PET ligands using in vivo LC-MS/MS (liquid chromatography coupled to mass spectrometry) and correlated these parameters with the reported PET ligand performance in nonhuman primates and humans available in the literature. The PET tracers studied included those reported to label G protein-coupled receptors (GPCRs), intracellular enzymes, and transporters. Additionally, data for each tracer was obtained from a mouse brain uptake assay (MBUA), previously published, where blood-brain barrier (BBB) penetration and clearance parameters were assessed and compared against similar data collected on a broad compound set of central nervous system (CNS) therapeutic compounds. The BP and SUV identified via nonradiolabeled LC-MS/MS, while different from the published values observed in the literature PET tracer data, allowed for an identification of initial criteria values we sought to facilitate increased potential for success from our early discovery screening paradigm. Our analysis showed that successful, as well as novel, clinical PET tracers exhibited BP of greater than 1.5 and peak SUVs greater than approximately 150% at 5 min post dose in rodents. The brain kinetics appeared similar between both techniques despite differences in tracer dose, suggesting linearity across these dose ranges. The assessment of tracers in a CNS exposure model, the mouse brain uptake assessment (MBUA), showed that those compound with initial brain-to-plasma ratios >2 and unbound fraction in brain homogenate >0.01 were more likely to be clinically successful PET ligands. Taken together, early incorporation of a LC/MS/MS cold tracer discovery assay and a parallel MBUA can be an useful screening paradigm to prioritize and rank order potential novel PET radioligands during early tracer discovery efforts. Compounds considered for continued in vivo PET assessments can be identified quickly by leveraging in vitro affinity and selectivity measures, coupled with data from a MBUA, primarily the 5 min brain-to-plasma ratio and unbound fraction data. Coupled utilization of these data creates a strategy to efficiently screen for the identification of appropriate chemical space to invest in for radiotracer discovery.

Prognostic value of FDG PET metabolic tumor volume in human papillomavirus-positive stage III and IV oropharyngeal squamous cell carcinoma.

The purpose of this study was to establish the prognostic utility in human papillomavirus (HPV)-positive stage III and IV oropharyngeal squamous cell carcinoma (SCC) of the (18)F-FDG parameters maximal, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). We included 70 patients in the present study who had a biopsy-proven HPV-positive (by in situ hybridization) stage III and IV oropharyngeal SCC and had a baseline PET/CT examination at our institution. Outcome endpoint was event-free survival (EFS), which included recurrence-free and overall survival. Cox proportional hazards multivariate regression analyses were performed. Survival analysis was performed using Kaplan-Meier survival curves. In Cox regression proportional hazard univariate analysis, total MTV (hazard ratio [HR], 1.02; p = 0.008), primary-tumor MTV (HR, 1.02; p = 0.024), neck nodal MTV (HR, 1.03; p = 0.006), neck nodal TLG (HR, 1.01; p = 0.006), and neck node status (HR, 4.45; p = 0.03) showed a statistically significant association with EFS. There was no statistically significant association of EFS with SUVmax, SUVmean, SUVpeak, and primary-tumor or overall TLG. In Cox regression proportional hazard multivariate model I, total MTV remained an independent prognostic marker for EFS when adjusted for every other variable individually in the model; in model II, primary-tumor MTV, neck node status, and SUVpeak are independent prognostic markers for EFS. The Kaplan-Meier survival curves using optimum cut point of 41 mL of total MTV were not significant (p = 0.09). Total MTV and primary-tumor MTV are associated with survival outcomes in patients with HPV-positive stage III and IV oropharyngeal SCC.

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). The mean (±SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97±3.16, 6.71±3.75, 10.05±5.37, 7.31±8.05 and 44.95±52.82, respectively. In univariate analyses, N category was associated with OS (P=0.037). Increased MTV ≥13ml was associated with decreased LRC and OS (P<0.0001). TLP ≥69.3g was also linked with both LRC and OS (P=0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P=0.035 and 0.049, respectively). Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

Pilot study of (89)Zr-bevacizumab positron emission tomography in patients with advanced non-small cell lung cancer.

BackgroundThe aim of this pilot study was to evaluate whether the uptake of 89Zr-bevacizumab in non-small cell lung cancer (NSCLC) tumors could be visualized and quantified. The correlation between tumor 89Zr-bevacizumab uptake and tumor response to antitumor therapy with a bevacizumab-based regimen was explored.MethodsSeven NSCLC patients underwent static PET scans at days 4 and 7 after injection of 36.4 ± 0.9 MBq (mean ± SD) 89Zr-bevacizumab, prior to commencing carboplatin-paclitaxel-bevacizumab chemotherapy (CPB). Overall survival (OS) and progression-free survival (PFS) to CPB followed by bevacizumab maintenance therapy was correlated to tumor tracer uptake, quantified using peak standardized uptake values (SUVpeak).ResultsZr-bevacizumab uptake (SUVpeak) was approximately four times higher in tumor tissues (primary tumor and metastases) than in non-tumor tissues (healthy muscle, lung, and fat) on days 4 and 7. A positive trend but no significant correlation could be found between SUVpeak and OS or PFS.ConclusionsThis pilot study shows that 89Zr-bevacizumab PET imaging in NSCLC is feasible. Further investigation to validate this technique as a predictive biomarker for selecting patients for bevacizumab treatment is warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0035-5) contains supplementary material, which is available to authorized users.

Quantitative evaluation of PET respiratory motion correction using real- time PET/MR simulated data.

The impact of respiratory motion correction on quantitative accuracy in PET imaging is evaluated using real-time simulations for variable patient specific characteristics such as tumor malignancy and respiratory pattern. Respiratory patterns from real patients were acquired, with long quiescent motion periods (type-1) as commonly observed in most of the patients and with long term amplitude variability as it is expected under conditions of difficult breathing (type-2). The respiratory patterns were combined with an MR-derived motion model to simulate real-time 4D PET/MR datasets. Lung and liver tumors were simulated with diameters ranging of 10 and 12 mm and tumor to background ratio ranging from 3:1 to 6:1. Projection data for 6 and 3 mm PET resolution were generated for Philips Gemini scanner and reconstructed without and with motion correction using OSEM (2 iterations, 23 subsets). Motion correction was incorporated into the reconstruction process based on MR-derived motion fields. Tumors peak standardized uptake values (SUVpeak) were calculated from thirty noise realizations. Respiratory motion correction improves the quantitative performance with the greatest benefit observed for patients of breathing type-2. For breathing type-1 after applying motion correction SUVpeak of 12 mm liver tumor with 6:1 contrast was increased by 46% for a current PET resolution (i.e. 6 mm) and 47% for a higher PET resolution (i.e. 3 mm). Furthermore, the benefit of higher scanner resolution is small for torso imaging unless motion correction is applied. In particular, for large liver tumor (12 mm) with low contrast (3:1) after motion correction the SUVpeak was 34% increased for 6 mm resolution and 50% increased for a higher PET resolution (i.e. 3 mm resolution. This investigation indicates high impact of respiratory motion correction on tumor quantitative accuracy and its importance in order to benefit from the increased resolution of future PET scanners.

Variability of average SUV from several hottest voxels is lower than that of SUVmax and SUVpeak.

To assess variability of the average standard uptake value (SUV) computed by varying the number of hottest voxels within an (18)F-fluorodeoxyglucose ((18)F-FDG)-positive lesion. This SUV metric was compared with the maximal SUV (SUV(max): the hottest voxel) and peak SUV (SUV(peak): SUV(max) and its 26 neighbouring voxels). Twelve lung cancer patients (20 lesions) were analysed using PET dynamic acquisition involving ten successive 2.5-min frames. In each frame and lesion, average SUV obtained from the N = 5, 10, 15, 20, 25 or 30 hottest voxels (SUV(max-N)), SUV(max) and SUV(peak) were assessed. The relative standard deviations (SDrs) from ten frames were calculated for each SUV metric and lesion, yielding the mean relative SD from 20 lesions for each SUV metric (SDr(N), SDr(max) and SDr(peak)), and hence relative measurement error and repeatability (MEr-R). For each N, SDr(N) was significantly lower than SDr(max) and SDr(peak). SDr(N) correlated strongly with N: 6.471 × N(-0.103) (r = 0.994; P < 0.01). MEr-R of SUV(max-30) was 8.94-12.63% (95% CL), versus 13.86-19.59% and 13.41-18.95% for SUV(max) and SUV(peak) respectively. Variability of SUV(max-N) is significantly lower than for SUV(max) and SUV(peak). Further prospective studies should be performed to determine the optimal total hottest volume, as voxel volume may depend on the PET system. • PET imaging provides functional parameters of (18) F-FDG-positive lesions, such as SUVmax and SUVpeak. • Averaging SUV from several hottest voxels (SUVmax-N) is a further SUV metric. • Variability of SUVmax-N is significantly lower than SUVmax and SUVpeak variability. • SUVmax-N should improve SUV accuracy for predicting outcome or assessing treatment response. • An optimal total hottest volume should be determined through further prospective studies.

Total lesion glycolysis as the best 18F-FDG PET/CT parameter in differentiating intermediate–high risk adrenal incidentaloma

Characterization of intermediate-high risk adrenal incidentaloma (AI) is important because biopsy or surgery should be performed to confirm the malignancy. We investigated which parameters of F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) had an additive role in distinguishing malignancies in patients with incidental adrenal masses of intermediate-high risk. From January 2008 to July 2013, 52 patients with a pathologically proven diagnosis of AI were retrospectively enrolled (age=56.4±12.7 years, M : F=34 : 18; benign : malignant=14 : 38). Volumetric parameters were size and volume according to combined CT, and metabolic parameters were peak standardized uptake value (SUV(peak)), maximum SUV (SUV(max)), mean SUV (SUV(mean)), and tumor-to-background ratio (SUV(max) of adrenal mass/SUV(mean) of liver). Metabolovolumetric parameters of metabolic tumor volume and total lesion glycolysis (TLG, SUV(mean)×metabolic tumor volume) were also included and compared with the diagnostic value. In addition, the highest diagnostic parameters among volumetric and metabolic parameters were combined and compared in terms of diagnostic accuracy. Compared with benign adrenal adenoma, malignant lesions showed significantly higher values of all (18)F-FDG PET/CT volumetric, metabolic, and metabolovolumetric parameters. Size showed the highest area under the curve (AUC) of 0.759 among the volumetric parameters, and SUV(peak) showed the highest AUC of 0.853 among the metabolic parameters. Among all the PET/CT parameters, TLG showed the highest AUC of 0.900, with a sensitivity of 92.1% and specificity of 78.6% at a cutoff of 12.0. The combined value of size and SUV(peak) showed lower diagnostic value than TLG. We found that TLG showed the best result in distinguishing intermediate-high risk AI among PET/CT parameters. TLG can be a useful PET/CT parameter for differential diagnosis of AI.

Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 × Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.

Uptake of (18)F-fluoro-2-deoxyglucose in the Healthy Testes of Young Men as Assessed by Positron Emission Tomography/Computed Tomography; Including the Inter- and Intra-observer Variation.

Knowledge of the physiological testicular accumulation of 18F-fluoro-2-deoxyglucose (FDG) is essential in order to discriminate between normal and pathological findings. In this study, the 18F-FDG-uptake in healthy testes of young men was assessed using positron emission tomography/computed tomography (PET/CT)-scans. A total of 40 testes of 20 men with a mean age of 26.5 ± 3.9 years were evaluated. 18F-FDG-uptake was expressed as the standardized uptake value (SUV). Testicular volume was measured on CT and PET. All scans were assessed by three researchers, one of whom assessed every scan twice. Laterality indices and inter- and intra-observer variation were evaluated. Correlation between the SUVmax and SUVpeak, between SUVmean and SUVpeak and between age and SUVpeak were assessed. Testes showed an average SUVmax of 3.42 ± 0.61, SUVpeak of 3.06 ± 0.54 and SUVmean of 2.44 ± 0.44. The average testicular volume on CT was 23.0 ± 6.4 ml, whereas on PET it was 18.0 ± 5.1 ml. Laterality indices were calculated of 0.077 ± 0.065 (SUVmax), 0.074 ± 0.066 (SUVpeak), 0.072 ± 0.063 (SUVmean), 0.245 ± 0.259 (CT), and 0.200 ± 0.188 (PET), respectively. Inter- and intra-observer reliability were found to be perfect for the SUVs (intraclass correlation coefficient [ICC] 0.992-1.0), but poor for testicular volumes (ICC 0.854-0.902). Testicular 18F-FDG uptake in young men can be measured accurately on PET/CT and shows high symmetry. Consequently, 18F-FDG PET/CT has the potential to become a useful instrument in the evaluation of the functioning of the individual testis.

PD1-10 ROLE OF POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY (PET/CT) IN THE EVALUATION OF THE METASTATIC ADRENAL MASSES

You have accessJournal of UrologyAdrenal1 Apr 2014PD1-10 ROLE OF POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY (PET/CT) IN THE EVALUATION OF THE METASTATIC ADRENAL MASSES Onur KAYGISIZ, Gokhun Ozmerdiven, Yakup Kordan, Burhan Coskun, Hakan Vuruskan, and Ismet Yavascaoglu Onur KAYGISIZOnur KAYGISIZ More articles by this author , Gokhun OzmerdivenGokhun Ozmerdiven More articles by this author , Yakup KordanYakup Kordan More articles by this author , Burhan CoskunBurhan Coskun More articles by this author , Hakan VuruskanHakan Vuruskan More articles by this author , and Ismet YavascaogluIsmet Yavascaoglu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.129AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the role of PET/CT imaging in the diagnosis of the patients with suspected non small cell lung cancer (NSCLC) metastases in the adrenal gland. METHODS Forty-one patients with suspected metastases Laparoscopic Adrenalectomy was performed in our clinic between March 2004 and July 2013. Fourteen patients without PET imaging were excluded from the study. The primary tumors in 22 were NSCLC. The parameters of the patients and peak standardized uptake values (SUVmax) were compared between the groups with benign and malignant pathologies. RESULTS Metastases were found in 17 adrenal masses (74%). Sex of the patient, sub-type of the lung cancer and the size of the adrenal mass were ineffective for the prediction of the metastasis (table). Together with this, the SUVmax value was found as significantly higher in the metastatic group (table). If the threshold value of SUV max for metastatic were taken as 3, sensitivity would be 100% and specificity would be 50%; whereas if the same value were taken as 4 or 5, sensitivity would be 88.2% and 76.5, respectively, and specificity would be 82.4% and 100%, respectively. CT or MRI were ineffective in determining the metastases (p=0,179). Specificity was 83.3%, while sensitivity was only 60%. However, in case we accepted the presence of suspicious metastasis based on CT or MRI as the criterion in the group we took the SUV max threshold value as 4, one patient more would be diagnosed to increase sensitivity to 94.11% and to decrease specificity to 66%. Likewise, taking the threshold SUV max value as 5 would allow diagnosing of 2 more patients and diagnosis of only 1 patient would be missed increasing sensitivity to 94.1% and lowering specificity to 83.3%. CONCLUSIONS In our series, PET/CT appears as an effective imaging modality to determine the adrenal metastases in patients with NSCLC as the primary disease. Follow-up may be considered in the first place for patients with SUV max values smaller than 3. SUVmax threshold value 5 sensitivity can be increased by combining with CT or MRI. Table. Comparison of the patients with primary NSCLC tumors in groups with and without metastasis Benign Grup 1 (n=6) Metastasis (Grup 2) (n=17) P Age (year)a 64,3±7,4 56,2± 7,8 0,047 SUVmaxa 2,8± 1,3 9,3±4,9 <0,001 Adrenal mass diameter (mm)a 26,0± 9,5 29± 15,5 0,617 Gender male 4 16 (80%) 0,155 female 2 1 (33,3%) Lung cancer subtypes Squamoz 3 7 (70%) 0,708 Adenocancer 3 10 (76,9%) CT/MRI benign 5 6 0,149 metastasis 1 9 SUV maxb ≤3 3 0 (0%) 0,011 > 3 3 17 (85%) SUV maxb ≤4 5 2 (28,6%) 0,003 > 4 1 15(93,8%) SUV maxb ≤5 6 3 (33,3%) 0,001 >5 0 14 (100%) SUVmax/ MRI-CT ≤5, benign 5 1 (16,7%) 0,001 > 5, metastasis 1 16 (94,1%) © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e13-e14 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Onur KAYGISIZ More articles by this author Gokhun Ozmerdiven More articles by this author Yakup Kordan More articles by this author Burhan Coskun More articles by this author Hakan Vuruskan More articles by this author Ismet Yavascaoglu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical Reasoning: A 49-year-old man with fever and proximal weakness of his arms

<b>44</b> <h3><b>Objectives:</b></h3> PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A), such as [¹¹C]UCB-J, allowed for the <i>in vivo</i> detection of synaptic density changes, which are correlated with a variety of neuropsychiatric diseases. We recently translated a novel SV2A radioligand, [¹⁸F]SynVesT-2 to human studies. The aim of this study was to evaluate the test-retest reproducibility of this SV2A tracer and the extent of specific binding in the brain through a blocking study. <h3><b>Methods:</b></h3> Five healthy volunteers were scanned on a High Resolution Research Tomograph (HRRT) scanner twice on different days, after injections of [¹⁸F]SynVesT-2. Two of the volunteers were also scanned following injection of levetiracetam (20 mg/kg, i.v.). Dynamic scans were 2-hours long with collection of arterial blood samples for measurements of the arterial input function (AIF) and plasma free fraction (<i>f</i>_p). Individual MR images were co-registered to a brain atlas to define the regions of interest (ROIs) for generation of time-activity curves (TACs), which were fitted with the 1-tissue compartment (1TC) model to derive regional distribution volumes (V_T). Regional nondisplaceable binding potential (<i>BP</i>_ND) was calculated from 1TC V_T values, using centrum semiovale (CS) as the reference region ¹. <h3><b>Results:</b></h3> [¹⁸F]SynVesT-2 was synthesized with high molar activity (189±83 MBq/nmol, n=12). Parent fraction of [¹⁸F]SynVesT-2 in plasma was 28±8% (n=12) at 30 min post injection (p.i.), which is similar to [¹¹C]UCB-J and [¹⁸F]SynVesT-1 ^2,3^,⁴. Plasma free fraction was high (<i>f</i>_p: 0.31±0.04, n=12), and also in line with those of [¹¹C]UCB-J and [¹⁸F]SynVesT-1 ^2,3. [¹⁸F]SynVesT-2 crossed the blood brain barrier quickly, with a peak standardized uptake value (SUV) of 8 in the thalamus and putamen at 7 min p.i. Regional TACs were fitted well with the 1TC model. And V_T values ranged from 2.0 mL/cm³ in the CS to 7.9 mL/cm³ in the putamen. The mean absolute test-retest variability (aTRV) for V_T was 5.5% across the 11 ROIs analyzed. Regional <i>BP</i>_ND values ranged from 3.00±0.32 in the putamen to 1.71±0.22 in the hippocampus, with a regional mean aTRV of 10.6%. The mean <i>BP</i>_ND values of [¹⁸F]SynVesT-2 are 78±5% of those of [¹¹C]UCB-J, 66±4% of [¹⁸F]SynVesT-1, and more than 2-fold higher than those of [¹⁸F]UCB-H ⁵.Shortening of the dynamic scan time from 2 h to 30 min had negligible impact (-0.3±4.3%) on <i>BP</i>_ND estimation. This is significantly shorter than the 60 min required for [¹¹C]UCB-J and [¹⁸F]SynVesT-1³. To eliminate arterial blood collection and simplify the scan protocol for multicenter clinical investigations, we evaluated the option of using SUVR-1 as a surrogate for <i>BP</i>_ND, by comparing the averaged SUVR-1 values from different imaging windows with the <i>BP</i>_NDvalues from the full dataset and found that the optimal static imaging window is 20-50 min p.i., with 1.2±1.6% difference between SUVR-1_{(20-50 min)}and <i>BP</i>_ND.Levetiracetam blocked 85% of the available SV2A binding sites, based on the Lassen plots. The estimated V_ND/<i>f</i>_p is 4.86 mL/cm³, indicating that about 20% of the tracer uptake in CS at baseline is attributable to specific uptake, which is lower than the 35-40% for [¹¹C]UCB-J ¹. <h3><b>Conclusions:</b></h3> The SV2A PET tracer [¹⁸F]SynVesT-2 demonstrated imaging characteristics in human brain suitable for large scale clinical trial investigations, with high brain uptake, fast kinetics, high specific binding, and low nonspecific uptake. Additionally, the pharmacokinetic properties of [¹⁸F]SynVesT-2 requires only a short 30 min dynamic scan to derive physiological parameters, or the use of a short static scan (20-50 min p.i.), to reliably estimate the specific binding without arterial blood collection.

Prognostic Value of Metabolic Parameters in Patients with Synchronous Colorectal Cancer Liver Metastasis Following Curative-Intent Colorectal and Hepatic Surgery

Synchronous colorectal cancer liver metastasis (SCLM) remains a clinical challenge, largely because of the limited availability of tools that use reliable prognostic indicators to guide treatment. This study assessed the prognostic ability of preoperative (18)F-FDG PET/CT in patients with SCLM who had undergone curative-intent colorectal and liver surgery. All included patients had undergone simultaneous colorectal and hepatic surgery to treat SCLM. Cox regression for survival analysis was undertaken using clinicopathologic variables and metabolic parameters (metabolic tumor volume [MTV], total lesion glycolysis [TLG], and peak standardized uptake value [SUVpeak]) as covariates, with tumor recurrence and death used as endpoints. One hundred twenty patients (82 men, 38 women; mean age ± SD, 59.9 ± 10.1 y) met the inclusion and exclusion criteria. Univariate analysis showed that MTV, TLG, and the size of hepatic metastases were significant indicators of both recurrence-free survival and overall survival, whereas those of primary colorectal tumors were not. Multivariate analysis revealed that the SUVpeak of primary tumors and hepatic metastases remained significant after adjusting for other clinicopathologic variables, whereas the MTV and TLG of hepatic metastases became insignificant after adjusting for differences in tumor size. The combination of a high SUVpeak of hepatic metastases and a low SUVpeak of primary tumors was related to poor prognosis under the multivariate model. In patients with SCLM who underwent curative-intent colorectal and liver surgery, metabolic parameters of hepatic metastases possess prognostic significance whereas those of primary colorectal tumors do not. For hepatic metastases, the SUVpeak is an independent prognostic factor, whereas MTV and TLG are surrogate measures of tumor size. Reduced recurrence-free survival rates are associated with higher SUVpeak for hepatic metastases and lower SUVpeak for primary tumors. Further studies are needed to elucidate the underlying mechanisms.

Tumor Texture Analysis in 18F-FDG PET: Relationships Between Texture Parameters, Histogram Indices, Standardized Uptake Values, Metabolic Volumes, and Total Lesion Glycolysis

Texture indices are of growing interest for tumor characterization in (18)F-FDG PET. Yet, on the basis of results published in the literature so far, it is unclear which indices should be used, what they represent, and how they relate to conventional indices such as standardized uptake values (SUVs), metabolic volume (MV), and total lesion glycolysis (TLG). We investigated in detail 31 texture indices, 5 first-order statistics (histogram indices) derived from the gray-level histogram of the tumor region, and their relationship with SUV, MV, and TLG in 3 different tumor types. Three patient groups corresponding to 3 cancer types at baseline were studied independently: patients with metastatic colorectal cancer (72 lesions), non-small cell lung cancer (24 lesions), and breast cancer (54 lesions). Thirty-one texture indices were studied in addition to SUVs, MV, and TLG, and 5 indices extracted from histogram analysis were also investigated. The relationships between indices were studied as well as the robustness of the various texture indices with respect to the parameters involved in the calculation method (sampling schemes and tumor volume of interest). Regardless of the patient group, many indices were highly correlated (Pearson correlation coefficient |r| ≥ 0.80), making it desirable to focus on only a few uncorrelated indices. Three histogram indices were highly correlated with SUVs (|r| ≥ 0.84). Four texture indices were highly correlated with MV, and none was highly correlated with SUVs (|r| ≤ 0.55). The resampling formula used to calculate texture indices had a substantial impact, and resampling using at least 32 discrete values should be used for texture indices calculation. The texture indices change as a function of the segmentation method was higher than that of peak and maximum SUVs but less than mean SUV for 5 texture indices and was larger than that of MV for 14 texture indices and for the 5 histogram indices. All these results were extremely consistent across the 3 tumor types and explained many of the observations reported in the literature so far. None of the histogram indices and only 17 of 31 texture indices were robust with respect to the tumor-segmentation method. An appropriate resampling formula with at least 32 gray levels should be used to avoid introducing a misleading relationship between texture indices and SUV. Some texture indices are highly correlated or strongly correlate with MV whatever the tumor type. Such correlation should be accounted for when interpreting the usefulness of texture indices for tumor characterization, which might call for systematic multivariate analyses.

Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification

The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUVpeak) over lesions of interest. Relative differences in SUVpeak between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUVpeak values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation when clinicians quantitatively assess PET/CT for therapy target definition and response assessment.

Differentiation of HIV-associated lymphoma from HIV-associated reactive adenopathy using quantitative FDG PET and symmetry

To determine the diagnostic accuracy of a semiautomated (18)F-FDG PET/CT measurement of total lesion glycolysis (TLG), maximum and peak standardized uptake value at lean body mass (SUL-Max and SUL-Peak), qualitative estimates of left/right nodal symmetry and FDG uptake for differentiating lymphoma from reactive adenopathy in HIV-infected patients. We retrospectively analyzed 41 whole-body (18)F-FDG PET/CT studies performed in HIV-infected patients for clinical reasons. The study received institutional review board approval. Of the 41 patients, 19 had biopsy-proven untreated lymphoma, and 22 with reactive adenopathy without malignancy on follow-up were used as controls. Nodal and extranodal visual qualitative metabolic scores, SUL-Max, SUL-Peak, CT nodal size, and PERCIST 1.0 threshold-based TLG and metabolic tumor volume (MTV) were determined. The qualitative intensity of nodal involvement and symmetry of uptake were compared using receiver operator curve (ROC) analysis. HIV plasma viral RNA measurements were also obtained. All of the quantitative PET metrics performed well in differentiating lymphoma from reactive adenopathy and performed better than qualitative visual intensity scores. The areas under the ROC curves (AUC) were significantly higher for TLG = 0.96, single SUL-Peak = 0.96, single SUL-Max = 0.97, and MTV = 0.96, compared to 0.67 for CT nodal size (p < 0.001). These PET metrics performed best in separating the two populations in aviremic patients, with AUCs of 1 (AUC 0.91 for CT nodal size). TLG, MTV, SUL-Peak and SUL-Max were more reliable markers among viremic individuals, with AUCs between 0.84 and 0.93, compared to other metrics. PET metrics were significantly correlated with plasma viral load in HIV-reactive adenopathy controls. Asymmetrical FDG uptake had an accuracy of 90.4 % for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Quantitative PET metabolic metrics as well as the qualitative assessment of symmetry of nodal uptake appear to be valuable tools for differentiating lymphoma from reactive adenopathy in HIV-infected patients using FDG PET. These parameters appear more robust in aviremic patients.

Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Livermean + (2 * Liversd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p &lt; 0.003) and TLG of 70.9 cm3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p &lt; 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.

Investigating the contribution of pre- and per-treatment 18F-FDG PET-CT segmentation methodologies for post-treatment tumor recurrence prediction in cervical cancer

Cervical cancer is one of the most common cancers to affect women worldwide. Despite the efficiency of radiotherapy treatment, some patients present post-treatment tumor recurrence, which increases the risk of death. Several studies suggest that tumor characteristics visible with PET imaging before and during the treatment could be used to predict post-treatment recurrence. We evaluate the contribution of pre- and per-treatment 18F-FDG PET images by exploring the predictive value of features extracted through several segmentation methods. Forty-one patients with locally advanced cervix cancer treated by chemoradiotherapy were considered. For each patient, two coregistered PET/CT scan were acquired before and during the treatment. A non-rigid registration was used to match the two PET acquisitions and evaluate the tumor metabolism inside the same area. Maximum and peak standardized uptake value (SUVmax and SUVpeak), the metabolic tumor volume (MTV) and the total lesion glycolysis (TLG) were evaluated. The predictive value of the extracted features was assessed through the Harrel's C-index. Results suggest that accurate segmentation can compute early meaningful features that are related with tumor recurrence. TLG seems to be strongly informative in prediction of tumor recurrence in cervical cancer.

Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial

In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC). Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Impact of Different Standardized Uptake Value Measures on PET-Based Quantification of Treatment Response

PET-based treatment response studies typically measure the change in the standardized uptake value (SUV) to quantify response. The relative changes of different SUV measures, such as maximum, peak, mean, or total SUVs (SUV(max), SUV(peak), SUV(mean), or SUV(total), respectively), are used across the literature to classify patients into response categories, with quantitative thresholds separating the different categories. We investigated the impact of different SUV measures on the quantification and classification of PET-based treatment response. Sixteen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor, resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), we acquired whole-body PET/CT scans at baseline, during treatment, and after treatment. The highest (18)F-FLT uptake lesions (~2/patient) were segmented on PET images. Tumor PET response was assessed via the relative change in SUV(max), SUV(peak), SUV(mean), and SUV(total), thereby yielding 4 different responses for each tumor at mid- and posttreatment. For each SUV measure, a population average PET response was determined over all tumors. Standard deviation (SD) and range were used to quantify variation of PET response within individual tumors and population averages. Different SUV measures resulted in substantial variation of individual tumor PET response assessments (average SD, 20%; average range, 40%). The most extreme variation between 4 PET response measures was 90% in individual tumors. Classification of tumor PET response depended strongly on the SUV measure, because different SUV measures resulted in conflicting categorizations of PET response (ambiguous treatment response assessment) in more than 80% of tumors. Variation of the population average PET response was considerably smaller (average SD, 7%; average range, 16%), and this variation was not statistically significant. Differences in tumor PET response were greatest between SUV(mean) and SUV(total) and smallest between SUV(max) and SUV(peak). Variations of tumor PET response at midtreatment and posttreatment were similar. Quantification and classification of PET-based treatment response in individual patients were strongly affected by the SUV measure used to assess response. This substantial uncertainty in individual patient PET response was present despite the concurrent robustness of the population average PET response. Given the ambiguity of individual patient PET responses, selection of PET-based treatment response measures and their associated thresholds should be carefully optimized.