F-FDG Standardized Uptake Value Research Articles

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.

Altered coupling between resting-state glucose metabolism and functional activity in epilepsy.

ObjectiveAltered functional activities and hypometabolism have been found in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE‐HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting‐state energy consumption and functional activities, but whether repeated seizures disturb the bioenergetic coupling and its relationship with seizure outcomes remain unknown.Methods 18F‐FDG PET and resting‐state functional MRI (rs‐fMRI) scans were performed with hybrid PET/MR in 26 patients with mTLE‐HS and in healthy controls. Energy consumption was quantified by 18F‐FDG standardized uptake value ratio(SUVR) relative to cerebellum. Spontaneous neural activities were estimated using regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF) from rs‐fMRI. Between‐group differences in SUVR and rs‐fMRI derived metrics were evaluated by two‐sample t test. Voxel‐wise spatial correlations were explored between SUVR and ReHo, fALFF across gray matter and compared between groups. Furthermore, the relationships between altered fALFF/SUVR and ReHo/SUVR coupling and surgical outcomes were evaluated.ResultsBoth the patients and healthy controls showed significant positive correlations between SUVR and rs‐fMRI metrics. Spatial correlations between SUVR and fMRI‐derived metrics across gray matter were significantly higher in patients with mTLE‐HS compared with healthy controls (fALFF/SUVR, P < 0.001; ReHo/SUVR, P = 0.022). Higher fALFF/SUVR couplings were found in patients who had Engel class IA after surgery than all other (P = 0.025), while altered ReHo/SUVR couplings (P = 0.097) were not.ConclusionThese findings demonstrated altered bioenergetic coupling across gray matter and its relationship with seizure outcomes, which may provide novel insights into pathogenesis of mTLE‐HS and potential biomarkers for epilepsy surgery planning.

Effect of hyperglycemia on brain and liver 18 F-FDG standardized uptake value (FDG SUV) measured by quantitative positron emission tomography (PET) imaging

Blood glucose is routinely measured prior to 18F-fluorodeoxyglucose (FDG) administration in positron emission tomography (PET) imaging to identify hyperglycemia that may affect image quality. In this study we explore the effects of blood glucose levels upon semi-quantitative standardized uptake value (SUV) measurements of target organs and tissues of interest and in particular address the relationship of blood glucose to FDG accumulation in the brain and liver. 436 FDG PET/CT consecutive studies performed for oncology staging in 229 patients (226 male) at the Ann Arbor Veterans Administration Healthcare System were reviewed. All patients had blood glucose measured (112.4±34.1mg/dL) prior to injection of 466.2±51.8MBq (12.6±1.4mCi) of FDG. SUV measurements of brain, aortic arch blood-pool, liver, and spleen were obtained at 64.5±10.2min' post-injection. We found a negative inverse relationship of brain SUV with increasing plasma glucose, levels for both absolute and normalized (either to blood-pool or liver) values. Higher blood glucose levels had a mild effect upon liver and blood-pool SUV. By contrast, spleen SUV was independent of blood glucose, but demonstrated the greatest variability (deviation on linear regression). In contrast to other tissues, liver and spleen SUV normalized to blood-pool SUV were not dependent upon blood glucose levels. The effects of hyperglycemia upon FDG uptake in brain and liver, over a range of blood glucose values generally considered acceptable for clinical PET imaging, may have measurable effects on semi-quantitative image analysis.

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis.

PurposeIn amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms.MethodsA new computational three-dimensional method to extract the spinal cord from 18F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, 18F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver.ResultsUptake of 18F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. 18F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis.ConclusionOur computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2-(F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC). The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separate time points. Dynamic PET/CT imaging recorded the uptake time course for both the tracers into osseous metastases. F-NaF and F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of F-NaF and F-FDG standardized uptake values (SUVs) images. Peak, mean, and total SUVs were evaluated for both tracers and all visible lesions. The F-NaF/F-FDG cocktail was optimized under the assumption that the contribution of both tracers to image formation is equal. SUV images from PET/CT imaging with a combination of F-NaF and F-FDG were generated for cocktail compositions with an F-NaF : F-FDG ratio varying from 1 : 8 to 1 : 2. The F-NaF peak and mean SUVs were on average four to five times higher than the F-FDG peak and mean SUVs, with an interlesion coefficient of variations of 20%. The total SUV for F-NaF was on average seven times higher than that for F-FDG. When the F-NaF : F-FDG ratio changed from 1 : 8 to 1 : 2, the typical SUV on the generated PET images increased by 50%, whereas the change in the uptake visual pattern was hardly noticeable. F-NaF and F-FDG in the cocktail contribute equally to image formation when the F-NaF : F-FDG ratio is 1 : 5. Therefore, we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the cocktail composition during any F-NaF/F-FDG cocktail PET/CT examination.

The reverse Warburg effect and 18F-FDG uptake in non-small cell lung cancer A549 in mice: a pilot study.

The purpose of this study was to observe the effect of fasting and feeding on (18)F-FDG uptake in a mouse model of human non-small cell lung cancer. In in vivo studies, (18)F-FDG small-animal PET scans were acquired in 5 mice bearing non-small cell lung cancer A549 xenografts on each flank with continuous feeding and after overnight fasting to observe the changes in intratumoral distribution of (18)F-FDG and tumor (18)F-FDG standardized uptake value (SUV). In ex vivo studies, intratumoral spatial (18)F-FDG distribution assessed by autoradiography was compared with the tumor microenvironment (including hypoxia by pimonidazole and stroma by hematoxylin and eosin stain). Five overnight-fasted mice and 5 fed mice with A549 tumors were observed. Small-animal PET scans were obtained in fed animals on day 1 and in the same animals after overnight fasting; the lapse was approximately 14 h. Blood glucose concentration after overnight fasting was not different from fed mice (P = 0.42), but body weight loss was significant after overnight fasting (P = 0.001). Intratumoral distribution of (18)F-FDG was highly heterogeneous in all tumors examined, and change in spatial intratumoral distribution of (18)F-FDG between 2 sets of PET images from the same mouse was remarkably different in all mice. Tumor (18)F-FDG mean SUV and maximum SUV were not significantly different between fed and fasted animals (all P > 0.05, n = 10). Only tumor mean SUV weakly correlated with blood glucose concentration (R(2) = 0.17, P = 0.03). In ex vivo studies, in fasted mice, there was spatial colocalization between high levels of (18)F-FDG uptake and pimonidazole-binding hypoxic cancer cells; in contrast, pimonidazole-negative normoxic cancer cells and noncancerous stroma were associated with low (18)F-FDG uptake. However, high (18)F-FDG uptake was frequently observed in noncancerous stroma of tumors but rarely in viable cancer cells of the tumors in fed animals. Host dietary status may play a key role in intratumoral distribution of (18)F-FDG. In the fed animals, (18)F-FDG accumulated predominantly in noncancerous stroma in the tumors, that is, reverse Warburg effect. In contrast, in fasted status, (18)F-FDG uptake was found in hypoxic cancer cells component (Pasteur effect). Our findings may provide a better understanding of competing cancer glucose metabolism hypotheses: the Warburg effect, reverse Warburg effect, and Pasteur effect.

Quantitative Volumetric CT-Histogram Analysis in N-Staging of 18F-FDG–Equivocal Patients with Lung Cancer

Lung cancer often coexists with acute and chronic lung diseases such as chronic obstructive pulmonary disease. Therefore, mediastinal lymph nodes may be false-positive on (18)F-FDG PET because of the inflammatory disease alone. Nevertheless, (18)F-FDG PET/CT is the primary imaging modality used for staging patients with lung cancer, including nodal status. The purpose of this study was to evaluate whether volumetric CT histogram analysis can improve the characterization of lymph nodes on PET/CT staging of patients with lung cancer. Sixty histologically proven lymph nodes of 45 patients aged 43-76 y diagnosed with lung cancer were investigated. (18)F-FDG PET/CT, contrast-enhanced CT, and nonenhanced CT were performed before surgery or biopsy as part of the clinical staging procedure. Lymph nodes were analyzed on the basis of the (18)F-FDG standardized uptake value and volumetric CT histogram analysis. These findings were correlated to the gold standard of histopathology. Histologic examination revealed 36 positive and 24 negative lymph nodes, which were also successfully analyzed by volumetric CT histogram. Median CT density was significantly higher for histologically positive lymph nodes (33.2 Hounsfield units [HU]; range, -29.8 to 59.1) than for histologically negative lymph nodes (10.1 HU; range, -21.0 to 87.4; P = 0.002). The incidence of malignancy was 88% above a cutoff value of 20 HU in the ten (18)F-FDG-equivocal lymph nodes; the incidence of benign findings was 100% in the interval between -20 and +20 HU. Visual- and density-based analysis on contrast-enhanced CT failed to differentiate affected from nonaffected lymph nodes. Three-dimensional histogram analysis is a promising and potentially valuable imaging surrogate for N-stage stratification in patients with lung cancer with unclear glucose uptake during (18)F-FDG PET imaging. In cases of equivocal (18)F-FDG PET status, this technique might potentially bridge the diagnostic gap between noninvasive techniques and invasive lymph node sampling and could help improve the yield of core biopsies.

18F-FES and 18F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

The aim of this study was to investigate the relationship between the tumor uptake of 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) and (18)F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors. Forty-seven patients with mesenchymal uterine tumors were studied with (18)F-FES and (18)F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERα, ERβ, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for (18)F-FES and (18)F-FDG were compared with the semiquantitative immunoreactive score (0-12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry. (18)F-FES uptake was significantly lower (P < 0.001) and the (18)F-FDG uptake and SUV ratio of (18)F-FDG to (18)F-FES ((18)F-FDG/(18)F-FES ratio) (P < 0.005 and P < 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERα, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between (18)F-FES SUV and immunohistochemistry scores of ERα, PR (P < 0.001), and PR-B (P < 0.005) as well as between (18)F-FDG SUV and GLUT-1 and Ki-67 (P < 0.001). However, the (18)F-FDG/(18)F-FES ratio showed significantly negative correlations with ERα, PR (P < 0.001), and PR-B (P < 0.005) and a positive correlation with Ki-67 LI (P < 0.001). In uterine sarcomas, ERα and (18)F-FES SUV showed a positive correlation (P < 0.001) in a low SUV range, and the (18)F-FDG/(18)F-FES ratio showed positive correlations with ERβ and GLUT-1 expression (P < 0.005). (18)F-FES and (18)F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The (18)F-FDG/(18)F-FES ratio was correlated with Ki-67, GLUT-1, and ERβ in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.

18F-FDG PET/CT Predicts Survival After Radioembolization of Hepatic Metastases from Breast Cancer

(90)Y radioembolization (selective internal radiation therapy [SIRT]) has emerged as a valuable therapeutic option in unresectable, chemotherapy-refractory hepatic metastases from breast cancer. The objective of the present study was to evaluate (18)F-FDG PET/CT for predicting survival in these patients. Fifty-eight consecutive patients with hepatic metastases from breast cancer were treated with SIRT. Before therapy, all patients underwent MRI of the liver. (18)F-FDG PET/CT was performed at baseline and 3 mo after SIRT to calculate percentage changes in maximum (18)F-FDG standardized uptake value (SUV(max)) relative to baseline. A decrease of more than 30% in the follow-up scan, compared with the baseline examination, indicated therapy response. Treatment response at 3 mo was also assessed in 43 patients using contrast-enhanced MRI and CT on the basis of the Response Evaluation Criteria in Solid Tumors. All patients were followed to complete survival data. Overall median survival after SIRT was 47 wk. Response as assessed with SUV(max) correlated significantly with survival after radioembolization, with responders having significantly longer survival (65 wk) than nonresponders (43 wk; P < 0.05). In multivariate analysis the change in SUV(max) was identified as the only independent predictor of survival (hazard ratio, 0.23; P < 0.005). Furthermore, a high pretherapeutic SUV(max) (>20) was associated with a significantly shorter median survival than was an SUV(max) of 20 or less (21 vs. 52 wk; P < 0.005). The presence of extrahepatic metastases (mean survival in both groups, 47 wk; P = 0.92), hormone receptor status (estrogen, P = 0.53; progesterone, P = 0.79; Her-2/neu, P = 0.49), and MRI/CT response (P = 0.91) did not predict survival. The change in SUV(max) as assessed by (18)F-FDG PET/CT before and 3 mo after SIRT was identified as the only independent predictor of survival in patients with hepatic metastases of breast cancer.

Single 20-Second Acquisition of Deep-Inspiration Breath-Hold PET/CT: Clinical Feasibility for Lung Cancer

This study was designed to compare tumor (18)F-FDG uptake between a single 20-s acquisition of deep-inspiration breath-hold PET/CT and free-breathing PET/CT for lung cancer. Before the clinical study, a phantom study was performed to determine the optimum breath-hold time for the PET scan. We studied 47 patients with lung cancer who underwent free-breathing PET/CT with the standard clinical protocol, followed by deep-inspiration breath-hold PET/CT of the thorax. In breath-hold PET/CT, the patients were asked to hold their breath in deep inspiration for 10 s during the CT scan and for 20 s during the PET scan. Maximum tumor (18)F-FDG standardized uptake value (SUVmax) was measured in free-breathing PET and breath-hold PET, and the percentage difference between these 2 values was calculated. Breath-hold PET showed a significant increase in SUVmax, as compared with free-breathing PET (8.26 +/- 4.59 vs. 11.25 +/- 7.24, P < 0.0001). The mean difference in SUVmax was 39.5% +/- 43.4%, and the range was 2.9%-248.3%. The difference in SUVmax was significant when compared between tumors in the upper lung (n = 22) and tumors in the lower lung (n = 25) (24.4% +/- 17.7% vs. 52.9% +/- 54.3%, P = 0.0077). The mean tumor size of the group with a high SUVmax difference (n = 13) was significantly smaller than that of the group with a low SUVmax difference (n = 34) (2.45 +/- 0.87 cm vs. 3.21 +/- 1.22 cm, P = 0.043), using a cutoff of 39.5%. The single 20-s acquisition of breath-hold PET/CT enabled more precise measurement of SUVmax, especially in the lower lung field and for small tumors, which may be affected by respiratory motion. This technique is feasible in the clinical setting and requires only a minor increase in examination time.

Combined Assessment of Metabolic and Volumetric Changes for Assessment of Tumor Response in Patients with Soft-Tissue Sarcomas

By allowing simultaneous measurements of tumor volume and metabolic activity, integrated PET/CT opens up new approaches for assessing tumor response to therapy. The aim of this study was to determine whether combined assessment of tumor volume and metabolic activity improves the accuracy of (18)F-FDG PET for predicting histopathologic tumor response in patients with soft-tissue sarcomas. Twenty patients with locally advanced high-grade soft-tissue sarcoma (10 men and 10 women; mean age, 49 +/- 17 y) were studied by (18)F-FDG PET/CT before and after preoperative therapy. CT tumor volume (CTvol) was measured by delineating tumor borders on consecutive slices of the CT scan. Mean and maximum (18)F-FDG standardized uptake value within this volume (SUVmean and SUVmax, respectively) were determined. Two indices of total lesion glycolysis (TLG) were calculated by multiplying tumor volume by SUVmean (TLGmean) and SUVmax (TLGmax). Changes in CTvol, SUVmean, SUVmax, TLGmean, and TLGmax after chemotherapy were correlated with histopathologic tumor response (> or =95% treatment-induced tumor necrosis). Accuracy for predicting histopathologic response was compared by receiver-operating-characteristic (ROC) curve analysis. Baseline SUVmax, SUVmean, CTvol, TLGmean, and TLGmax were 11.22 g/mL, 2.84 g/mL, 544.1 mL, 1,619.8 g, and 8852.9 g, respectively. After neoadjuvant therapy, all parameters except CTvol showed a significant decline (DeltaSUVmax = -51%, P < 0.001; DeltaSUVmean = -40%, P < 0.001; DeltaCTvol = -14%, P = 0.37; DeltaTLGmean = -44%, P = 0.006; and DeltaTLGmax = -54%, P = 0.001). SUV changes in histopathologic responders (n = 6) were significantly more pronounced than those in nonresponders (n = 14) (P = 0.001). Histopathologic response was well predicted by changes in SUVmean and SUVmax (area under ROC curve [AUC] = 1.0 and 0.98, respectively) followed by TLGmean (AUC = 0.77) and TLGmax (AUC = 0.74). In contrast, changes in CTvol did not allow prediction of treatment response (AUC = 0.48). In this population of patients with sarcoma, TLG was less accurate in predicting tumor response than were measurements of the intratumoral (18)F-FDG concentration (SUVmax, SUVmean). Further evaluation of TLG in larger patient populations and other tumor types is necessary to determine the value of this conceptually attractive parameter for assessing tumor response.

Comparison of Tumor Volumes Derived from Glucose Metabolic Rate Maps and SUV Maps in Dynamic 18F-FDG PET

Tumor delineation using noninvasive medical imaging modalities is important to determine the target volume in radiation treatment planning and to evaluate treatment response. It is expected that combined use of CT and functional information from 18F-FDG PET will improve tumor delineation. However, until now, tumor delineation using PET has been based on static images of 18F-FDG standardized uptake values (SUVs). 18F-FDG uptake depends not only on tumor physiology but also on blood supply, distribution volume, and competitive uptake processes in other tissues. Moreover, 18F-FDG uptake in tumor tissue and in surrounding healthy tissue depends on the time after injection. Therefore, it is expected that the glucose metabolic rate (MRglu) derived from dynamic PET scans gives a better representation of the tumor activity than does SUV. The aim of this study was to determine tumor volumes in MRglu maps and to compare them with the values from SUV maps. Twenty-nine lesions in 16 dynamic 18F-FDG PET scans in 13 patients with non-small cell lung carcinoma were analyzed. MRglu values were calculated on a voxel-by-voxel basis using the standard 2-compartment 18F-FDG model with trapping in the linear approximation (Patlak analysis). The blood input function was obtained by arterial sampling. Tumor volumes were determined in SUV maps of the last time frame and in MRglu maps using 3-dimensional isocontours at 50% of the maximum SUV and the maximum MRglu, respectively. Tumor volumes based on SUV contouring ranged from 1.31 to 52.16 cm3, with a median of 8.57 cm3. Volumes based on MRglu ranged from 0.95 to 37.29 cm3, with a median of 3.14 cm3. For all lesions, the MRglu volumes were significantly smaller than the SUV volumes. The percentage differences (defined as 100% x (V MRglu - V SUV)/V SUV, where V is volume) ranged from -12.8% to -84.8%, with a median of -32.8%. Tumor volumes from MRglu maps were significantly smaller than SUV-based volumes. These findings can be of importance for PET-based radiotherapy planning and therapy response monitoring.

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-18F-Fluorothymidine and 18F-FDG

Some new radiotracers might add useful information and improve diagnostic confidence of (18)F-FDG imaging in tumors. A multicenter clinical trial was designed to investigate the diagnostic performance of dual-tracer ((18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]) PET/CT in pulmonary nodules. Fifty-five patients underwent dual-tracer imaging in 6 imaging centers using the same models of equipment and standardized protocols. The images were interpreted by a collective group of readers who were unaware of the clinical data. The diagnostic performance using either tracer alone or dual-tracers together, with or without CT, was compared. The histological diagnosis or clinical findings in a 12-mo follow-up period served as the standard of truth. In 16 patients with malignant tumor, 16 with tuberculosis, and 23 with other benign lesions, the sensitivity and specificity of (18)F-FDG and (18)F-FLT were 87.5% and 58.97% and 68.75% and 76.92%, respectively. The combination of dual-tracer PET/CT improved the sensitivity and specificity up to 100% and 89.74%. The 3 subgroups of patients could be best separated when the (18)F-FLT/(18)F-FDG standardized uptake value ratio of 0.4-0.90 was used as the threshold. By reflecting different biologic features, the dual-tracer PET/CT using (18)F-FDG and (18)F-FLT favorably affected the diagnosis of lung nodules.

Uptake of 18F-Fluorocholine, 18F-FET, and 18F-FDG in C6 Gliomas and Correlation with 131I-SIP(L19), a Marker of Angiogenesis

Targeting extracellular structures that are involved in angiogenic processes, such as the extra domain B of fibronectin, is a promising approach for the diagnosis of solid tumors. The aim of this study was to determine uptake of the (18)F-labeled PET tracers (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium), (18)F-fluoro-ethyl-l-tyrosine (FET), and (18)F-FDG in C6 gliomas of the rat and to correlate it with uptake of the anti-extra domain B antibody (131)I-SIP(L19) as a marker of neoangiogenesis. C6 gliomas were orthotopically induced in 17 rats. Uptake of all tracers was measured using quantitative autoradiography, and uptake of (18)F-fluorocholine, (18)F-FET, and (18)F-FDG was correlated with uptake of (131)I-SIP(L19) on a pixelwise basis. The mean (131)I-SIP(L19), (18)F-fluorocholine, (18)F-FET, and (18)F-FDG standardized uptake values in the tumor and the contralateral normal cortex (in parentheses) were 0.31 +/- 0.22 (not detectable), 2.00 +/- 0.53 (0.49 +/- 0.07), 3.67 +/- 0.36 (1.42 +/- 0.22), and 7.23 +/- 1.22 (3.64 +/- 0.51), respectively. The (131)I-SIP(L19) uptake pattern correlated best with (18)F-fluorocholine uptake (z = 0.80, averaged z-transformed Pearson correlation coefficient) and (18)F-FET uptake (z = 0.79) and least with (18)F-FDG (z = 0.37). One day after intravenous injection, (131)I-SIP(L19) displayed a very high tumor-to-cortex ratio, which may be used in the diagnostic work-up of brain tumor patients. Of the 3 investigated (18)F tracers, (18)F-fluorocholine and (18)F-FET correlated better with the pattern of (131)I-SIP(L19) uptake than did (18)F-FDG. Whether this means that (18)F-fluorocholine and (18)F-FET are better suited than (18)F-FDG to monitor antiangiogenic therapy should be investigated in future studies.