fluoro-2-deoxy-D-glucose Positron Emission Tomography Studies Research Articles

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy

Background: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. Methods: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2’-[¹⁸F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BP_ND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. Results: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. Conclusion: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

Glucose metabolism in normal aging and Alzheimer’s disease: methodological and physiological considerations for PET studies

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder associated with progressive loss of cognitive function. 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has long been used to measure resting-state cerebral metabolic rates of glucose, a proxy for neuronal activity. Several FDG PET studies have shown that metabolic reductions occur decades before onset of AD symptoms, suggesting that metabolic deficits may be an upstream event in at least some late-onset AD cases. This review explores this possibility, initially discussing the link between AD pathology, neurodegeneration, oxidative stress and AD, and then discussing findings of FDG PET hypometabolism in AD patients as well as in at-risk individuals, especially those with a first-degree family history of late-onset AD. While the rare early-onset form of AD is due to autosomal dominant genetic mutations, the etiology and pathophysiology of age-dependent, late-onset AD is more complex. Recent FDG PET studies have shown that adult children of AD-affected mothers are more likely than those with AD-fathers to show AD-like brain changes. Given the connection between glucose metabolism and mitochondria, and the fact that mitochondrial DNA is maternally inherited in humans, it is here argued that altered bioenergetics may be an upstream event in those with a maternal history of late-onset AD. Biomarkers of AD have great potential for identifying AD endophenotypes in at-risk individuals, which may help direct investigation of potential susceptibility genes.

EEG-based vigilance and cerebral glucose metabolism – a parallel EEG and FDG PET study

Introduction: Patients with Alzheimer's disease (AD) compared to controls can be characterized by a pattern of reduced glucose metabolism in temporoparietal, posterior cingulate, and frontal cortices using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). Sleep studies demonstrated an altered glucose metabolism in some of the respective cortices during the transition from wake to sleep. While sleep can be excluded during the examination, drowsiness may still bias the glucose metabolism of these patients during the FDG PET. Methods: In the present study, a sample of 10 patients with probable AD (53–76 years, 3 women) was investigated with simultaneous EEG PET (FDG). According to the drowsiness level the sample was median split into a group with stable and unstable EEG-vigilance, respectively. Imaging analyses were performed in SPM5. Results: Patients with stable compared to unstable EEG-vigilance showed an increased glucose metabolism in the lateral superior temporal gyrus (p=.001 uncorrected, k=30). Patients with unstable compared to stable EEG-vigilance showed an increased glucose metabolism in the lateral and medial frontal gyrus, and the median cingulate gyrus (p=.001 uncorrected, k=30). Conclusion: These preliminary results demonstrate the potential of EEG-vigilance to modulate the cerebral glucose metabolism in AD during FDG PET.

Comparison of diffusion‐weighted MRI and 2‐[fluorine‐18]‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) for detecting primary colorectal cancer and regional lymph node metastases

To examine the usefulness of diffusion-weighted MRI (DW-MRI) for the detection of both primary colorectal cancer and regional lymph node metastases, and compare its performance with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the same patients. We studied 25 patients with known colorectal cancer. All underwent both DW-MRI and FDG-PET studies. The images were retrospectively assessed by visual inspection and the imaging findings were compared with histopathological findings on surgical specimens. Of the 27 primary colorectal lesions surgically excised in 25 patients, 23 (85.2%) were true-positive on both DW-MRI and FDG-PET. Two cancers were false-negative on DW-MRI but true-positive on FDG-PET, and two were false-negative on both DW-MRI and FDG-PET. With respect to the detectability of metastatic lymph nodes, DW-MRI and FDG-PET manifested a sensitivity of 80% (8/10) and 30.0% (3/10), a specificity of 76.9% (10/13) and 100% (13/13), and an accuracy of 78.3% (18/23) and 69.6% (16/23), respectively. DW-MRI is inferior to FDG-PET for the detection of primary lesions, but superior for the detection of lymph node metastases.

FDG-PET of patients with suspected renal failure: standardized uptake values in normal tissues

This study aims to clarify the effect of renal function on 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging and determine the clinical significance of renal function in this setting. We compared FDG distribution between normal volunteers and patients with suspected renal failure. Twenty healthy volunteers and 20 patients with suspected renal failure who underwent FDG-PET between November 2002 and May 2005 were selected for this study. We define "patients with suspected renal failure" as having a blood serum creatinine level in excess of 1.1 mg/dl. The serum creatinine level was examined once in 2 weeks of the FDG-PET study. Regions of interest were placed over 15 regions for semi-quantitative analysis: the white matter, cortex, both upper lung fields, both middle lung fields, both lower lung fields, mediastinum, myocardium of the left ventricle, the left atrium as a cardiac blood pool, central region of the right lobe of the liver, left kidney, and both femoris muscles. The mean standardized uptake values (SUVs) of brain cortex and white matter were higher in healthy volunteers than in renal patients. The mean SUVs of the mediastinum at the level of the aortic arch and left atrium as a cardiac blood pool were lower in healthy volunteers than in patients with suspected renal failure. These regions differed between healthy volunteers and patients with suspected renal failure (P < 0.05). We found decreasing brain accumulation and increasing blood pool accumulation of FDG in patients with high plasma creatinine. Although the difference is small, this phenomenon will not have a huge effect on the assessment of FDG-PET imaging in patients with suspected renal failure.

Statistical Image Analysis of Cerebral Glucose Metabolism in Patients with Cognitive Impairment following Diffuse Traumatic Brain Injury

The aim of this study was to explore the regional cerebral glucose metabolism (rCM) in patients with chronic stage traumatic brain injury (TBI) compared with normal controls. We also investigated the relationship between regional cerebral glucose metabolism and cognitive function. We performed 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) study using statistical parametric mapping (SPM) analysis in 36 diffuse axonal injury (DAI) patients (mean age +/- SD, 36.3 +/- 9.8 years). At 6 months or more after head injury, all patients underwent FDG-PET study and neuropsychological batteries to assess cognitive function. Thirty healthy, gender-matched control subjects who were comparable in age were also studied. Between the TBI patients and normal controls, group comparisons showed regional metabolic decreases in the bilateral frontal lobes, temporal lobes, thalamus, as well as the right cerebellum in the TBI group. Only full-scale Intelligence Quotient (IQ) (mean +/- SD, 78.5 +/- 11.9) correlated positively with rCM in the right cingulate gyrus and the bilateral medial frontal gyrus. In other examinations, the correlation was not provided. DAI may induce functional disconnection and decreased neuronal activity, and finally lead to diffuse glucose hypometabolism. Low full-scale IQ scores may be related to significantly different underlying cognitive impairment. In supporting cognitive function following TBI, which showed diffuse cerebral metabolic reduction compared with normal controls, medial prefrontal cortex and anterior cingulate cortex may be an important component.

Positron emission tomography and bone metastases

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?

Brain glucose metabolism in the early and specific diagnosis of Alzheimer?s disease

The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer's disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities.

FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma.

Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control.

High uptake of L-3-[123I]iodo-alpha-methyl tyrosine in pilocytic astrocytomas.

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[123I]iodo-alpha-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n = 10, r = 0.87, P < 0.05). Differences in IMT uptake in primaries (1.7 +/- 0.6, n = 10) and in recurrent tumours (2.3 +/- 0.7, n = 6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.

Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy- d-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Germ cell tumor: differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling.

To evaluate the feasibility of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor (GCT) to monitor treatment and differentiate residual masses after chemotherapy. Twenty-six FDG PET studies were performed in 21 patients with GCT, FDG uptake of tumors was interpreted visually, and the lean standardized uptake value (SUVlean) was determined. Tumor kinetic rate constants (K1, k2, k3) and net rate of FDG phosphorylation (K = [K1.k3]/[k2 + k3]) in tumors were calculated from the dynamic data by means of a three-compartment model, assuming k4 = 0. Viable tumors (n = 10) showed intense FDG uptake and could easily be differentiated visually from mature teratoma (n = 6) and necrosis or scar (n = 10). The SUVlean of residual viable tumors (4.51 +/- 1.34 [mean +/- SD]) was higher than that of mature teratoma (1.38 +/- 0.71) and necrosis or scar (1.05 +/- 0.29) (P < .05). Although neither the visual interpretation nor SUVlean differentiated mature teratoma from necrosis or scar, there were statistically significant differences in the kinetic rate constants K1 and K between mature teratoma and necrosis or scar as follows: K1, 0.113 mL/min/g +/- 0.026 versus 0.036 mL/min/g +/- 0.005 (P < .05); K, 0.005 mL/min/g +/- 0.003 versus 0.0008 mL/min/g +/- 0.0001 (P < .05). FDG PET with kinetic analysis appears to be a promising method for management of disease in patients with GCT after treatment.

Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors.

To assess the usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) of the head and neck in locating occult primary lesions in patients with metastatic cervical adenopathy. Seventeen patients with metastatic cervical adenopathy of unknown primary origin were referred for FDG PET of the head and neck. All patients had undergone correlative anatomic imaging within 1 month of FDG PET. Surgical, clinical, and histopathologic findings were used to assess the performance of FDG PET. Increased apical lung uptake at FDG PET led to a biopsy-proved diagnosis of primary lung cancer in two patients. Of the remaining 15 patients, 10 had a focus of increased activity; directed biopsy of these sites led to confirmation of a primary carcinoma in seven patients. Correlative anatomic imaging failed to demonstrate the primary sites of disease in two of these seven patients. None of the five patients with negative FDG PET studies have manifested evidence of a primary site of disease during follow-up of 8-42 months (mean, 29 months). FDG PET allows effective localization of the unknown primary site of origin in metastatic head and neck cancer and can contribute substantially to patient care.

Detection of Residual Tumours in Postchemotherapy Testicular Cancer by FDG-PET

The aim of this study was to investigate whether 2-(F-18)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) could reliably detect testicular cancer in patients following chemotherapy. Twenty FDG-PET studies were performed on 15 patients with metastatic seminoma or non-seminoma. Tracer uptake in the PET study was measured by calculating the standardised uptake value (SUV) for the tracer. Nine lesions out of 20 were judged to be positive based on high FDG uptake. Three proved to represent inflammatory changes in non-cancerous tissue. Eleven PET studies were negative. In one of these, viable tumour was found at retroperitoneal lymphadenectomy. The median SUV values of metastatic tumours and benign residual tumours were 2.7 (range 1.6-9.5, n= 10) and 1.7 (range 0.7-5.5, n= 15), respectively. The large overlap of SUVs between these groups was due to the relatively high FDG uptake in inflammatory tissue (median 4.2, range 2.0-5.5, n = 4). The results indicate that FDG imaging of metastatic testicular cancer after chemotherapy has limited value because of a potentially high accumulation of FDG in inflammatory tissues. @ 1997 Published by Elsevier Science Ltd.

Cerebral metabolic rate for glucose during the first six months of life: an FDG positron emission tomography study.

To measure the local cerebral metabolic rate for glucose (LCMRGlc) in neonatal brains during maturation using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Twenty infants were studied using PET during the neonatal period. The postconceptional age ranged from 32.7 to 60.3 weeks. All infants had normal neurodevelopment and were normoglycaemic. The development of the infants was carefully evaluated (follow up 12-36 months) clinically, and by using a method based on Gesell Amatruda's developmental diagnosis. LCMRGlc was quantitated using PET derived from FDG kinetics and calculated in the whole brain and for regional brain structures. LCMRGlc for various cortical brain regions and the basal ganglia was low at birth (from 4 to 16 mumol/100 g/minute). In infants 2 months of age and younger LCMRGlc was highest in the sensorimotor cortex, thalamus, and brain stem. By 5 months, LCMRGlc had increased in the frontal, parietal, temporal, occipital and cerebellar cortical regions. In general, the whole brain LCMRGlc correlated with postconceptional age (r = 0.90; P < 0.001). The change in the glucose metabolic pattern observed in the neonatal brain reflects the functional maturation of these brain regions. These findings show that LCMRGlc in infants increases with maturation. Accordingly, when LCMRGlc is measured during infancy, the postconceptional age has to be taken into account when interpretating the results.

Head and neck cancer: detection of recurrence with PET and 2-[F-18]fluoro-2-deoxy-D-glucose.

To evaluate positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in detection of suspected recurrence of head and neck cancer, and to compare visual, static, and kinetic analyses of the tracer uptake. Seventeen dynamic FDG PET studies were performed in 15 patients. The images were interpreted visually, and the uptake was quantitated as the standardized uptake value (SUV) and as the regional FDG metabolic rate. Sensitivity of blinded visual interpretation of the PET images for the presence of malignancy was 88% and specificity was 86%. Malignant lesions accumulated significantly more FDG than benign lesions (P = .008 for SUVs, P = .002 for regional metabolic rates). When maximum uptake of FDG in the benign lesions was used as a threshold, the sensitivity of SUV analysis for malignancy was 75% and that of regional metabolic rates was 86%. Detection of recurrent head and neck cancer is feasible with FDG PET. Quantitation of FDG uptake assists in correct interpretation of the PET images.