Measurement of myocardial glucose uptake in patients with ischemic cardiomyopathy: application of a new quantitative method using regional tracer kinetic information.
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Quantification of myocardial glucose uptake (MGU) by 18F-fluoro-2-deoxyglucose (FDG) using PET may be inaccurate, because the correction factor that relates myocardial FDG uptake to MGU, the lumped constant (LC), is not a true constant. Recent studies have shown that analysis of FDG time-activity curves allows determination of individual LCs and that variable LCs yield accurate determination of MGU. We compared the magnitude of the LC in different regions of the heart in patients with ischemic cardiomyopathy. METHODS: Twenty patients with ischemic cardiomyopathy and an average ejection fraction of 33% underwent dynamic 13N-ammonia and FDG PET. We determined myocardial perfusion and MGU in 177 regions classified as control (71 regions), mismatch (50 regions) and match (56 regions), according to findings on PET and echocardiography. Regional MGU was calculated with both regional LCs and a fixed LC of 0.67. RESULTS: All results were expressed as mean +/- SD. Myocardial perfusion was highest in control regions (0.52+/-0.18 mL/g/min), reduced in mismatch regions (0.43+/-0.19 mL/g/min; P < 0.05 versus control) and severely reduced in match regions (0.28+/-0.17 mL/g/min; P < 0.001 versus control and mismatch). Regional LCs ranged from 0.45 to 1.30 and differed between patients (P < 0.001). Regional LCs were similar in regions diagnosed as control (0.78+/-0.23), mismatch (0.80+/-0.24) and match (0.72+/-0.21). MGU (micromol/g/min) calculated by regional LCs was similar in control (0.52+/-0.16) and mismatch (0.49+/-0.19) regions and decreased in match regions (0.31+/-0.12, P < 0.001). The agreement between MGU calculated with variable and fixed LCs was poor. CONCLUSION: The LC used in the calculation of MGU was not affected by regional differences in the metabolic state of the myocardium. However, the LC varied substantially between patients in control, mismatch and match regions. These findings indicate that quantitative measurements of MGU using a fixed LC must be interpreted with caution. (+info)
Optimization of urinary FDG excretion during PET imaging.
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Accumulation of fluorodeoxyglucose (FDG) activity in the urine interferes with the visualization of pelvic and, sometimes, abdominal abnormalities. Although this is a major problem, there are few data on the physiological variables affecting FDG urinary excretion that are critical to minimizing urinary FDG interference during PET imaging. METHODS: The excretion of FDG in urine was determined during 90 min in four groups of rats (n = 24) under the following conditions: normal, hydrated, hydrochlorothiazide treated and phlorizin treated. FDG clearance rates were measured in both normal and phlorizin-treated animals and compared with the glomeruler filtration rate measured with 99mTc-diethylenetriamine pentaacetic acid. We measured FDG excretion in 10 patients who had no known renal disease and were undergoing PET scanning (divided into two groups: hydrated and dehydrated) to relate the animal data to humans. RESULTS: The hydrated and phlorizin-treated animals had the highest excretion of FDG (39.68+/-5.00 % injected dose (%ID) and 45.64+/-9.77 %ID, respectively). Animals given the hydrochlorothiazide had the highest urinary volume, but the percentage excreted was comparable with the normal rats. Measurement of the clearance of FDG in animals before and after the administration of phlorizin determined the amount of FDG reabsorbed in the proximal tubules to be 56%+/-9.15%. The hydrated patients had a higher excretion of FDG than dehydrated patients (16.98+/-1.99 %ID versus 14.27+/-1.00 %ID, P < 0.021), and the volume of urine voided was significantly higher (P < 0.020). CONCLUSION: Hydrochlorothiazide increases urine volume without enhancing FDG excretion. The hydration of patients before PET scanning may lead to more FDG reaching the bladder. Reduction of bladder activity by more frequent voiding facilitated by increased urine volume in hydrated patients may be offset by increased delivery of FDG to the bladder. A preferable means of increasing urinary volume without increasing delivery of FDG to the bladder may be the use of a diuretic. (+info)
A mathematical model for the distribution of fluorodeoxyglucose in humans.
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The goals of this study were to define the total body distribution kinetics of 18F-fluorodeoxyglucose (FDG), to contribute to its radiation dosimetry and to define a suitable proxy for arterial cannulation in human FDG studies. METHODS: Time-activity FDG heart, lung, liver and blood data from paired fasting and glucose-loaded sessions in five adult human volunteers, together with published brain parameters, were incorporated into a multicompartmental model for whole-body FDG kinetics. Tau values were calculated from this model. We also compared the usefulness of activity in the left ventricle (LV), right ventricle (RV), left lung and right lung as proxy for arterial blood FDG sampling. RESULTS: No systematic difference was found in model parameters between the fasting and glucose-fed sessions, even for the parameter for transfer of FDG into the myocardium. Myocardial PET data fitted well to a model in which there is very rapid exchange indistinguishable from blood kinetics and transfer into an intracellular "sink." The lung data fitted to a simple sink representing the lung cells. The liver data required an additional intermediate exchange compartment between the plasma and a hepatic sink. In terms of total body distribution kinetics, unmeasured organs and tissues (probably the skeletal muscle and gut) become increasingly important with time and account for a mean of 76% of the decay-corrected FDG activity at infinity. Right lung activity, corrected to venous blood, represents the whole arterial blood curve better than the LV or RV. The tau values for radiation dosimetry of FDG in the heart, lungs, liver and bladder calculated from our model do not differ significantly from published results using other methods. Bladder tau decreased with voiding frequency and was markedly decreased with early voiding. CONCLUSION: Glucose loading state is not a good predictor of myocardial FDG uptake. The majority of FDG distribution at 90 min is in tissues other than the blood, brain, heart and liver. Bladder radiation will be much reduced if the patient voids early after FDG administration. Summed large volume right lung activity, normalized to venous blood activity, is a good proxy for arterial blood FDG sampling. The model presented may be expanded to include other FDG kinetics as studies become available. (+info)
FDG-PET in the staging work-up of patients with suspected intracranial metastatic tumors.
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OBJECTIVE: To evaluate the role of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose (FDG-PET) in 31 patients with evidence of intracranial metastatic disease. MATERIALS AND METHODS: PET was used to evaluate the intracranial lesions for glucose hypermetabolism to suggest malignancy, mutiplicity of intracranial lesions, and extracranial foci or sources of disease. Patients with proven malignant intracranial lesions subsequently underwent further corroborative radiologic tests and histologic examination to confirm staging and primary location. RESULTS: PET identified focal hypermetabolic abnormalities in 19 of 22 intracranial metastases, 2 hypometabolic lesions, and 1 renal cell tumor embolism that hemorrhaged (hypometabolic lesion). It also identified 82% of extracranial primary tumor sites, of which 55% were found only on PET and not on conventional diagnostic tests. CONCLUSION: FDG-PET may prove valuable in the initial work-up of patients with suspected intracranial metastases. (+info)
Quantification of glucose transport and phosphorylation in human skeletal muscle using FDG PET.
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PET with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is used for quantifying glucose metabolism in brain and myocardium in vivo. We developed and validated a similar procedure for the quantification of the two initial steps of glucose metabolism in skeletal muscle in vivo. METHODS: The measurement protocol was first optimized by computer simulations. In addition to the accuracy in sampling plasma input and tissue time-activity curves, precise determination of the fractional blood volume, that is, the extracellular tissue volume fraction, plays a key role in correctness of the determined model constants. The optimized protocol was subsequently used to estimate transmembrane muscular glucose transport and hexokinase activity in six human subjects with normal or altered glucose utilization. PET was performed during the steady state of an euglycemic hyperinsulinemic clamp. RESULTS: A three-compartment model provides a better description of the experimental data than a two- or four-compartment model. Glucose clearance from the extracellular compartment into the skeletal muscle cell (K1) ranges from 0.024 to 0.093 mL/g/min. The intracellular glucose phosphorylation rate (k3) varies between 0.030 and 0.142 min(-1). The regional muscular glucose utilization, as calculated from the determined model parameters, lies between 10.7 and 83.3 micromol/kg/min and correlates with the whole-body glucose utilization as independently determined (R2 = 0.83; P < or = 0.01). CONCLUSION: We demonstrate by computer simulations that a three-compartment model can be used to characterize the first two steps of glucose metabolism in skeletal muscle. An optimized measurement protocol is developed and applied to experimental data. This experimental approach should be appropriate to test whether glucose transport or hexokinase activity is altered in disorders of muscular glucose utilization. (+info)
Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan.
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The management of metastatic thyroid carcinoma patients with a negative 131I scan presents considerable problems. Fifty-four athyrotic papillary thyroid carcinoma patients whose 1311 whole-body scans were negative underwent 18F-fluorodeoxyglucose (FDG) PET; the purpose was to determine whether this procedure could localize metastatic sites. We also assessed its usefulness in the management of these patients. METHODS: Whole-body emission scan was performed 60 min after the injection of 370-555 MBq 18F-FDG, and additional regional attenuation-corrected scans were obtained. Metastasis was pathologically confirmed in 12 patients and was confirmed in other patients by overall clinical evaluation of the findings of other imaging studies and of the subsequent clinical course. RESULTS: In 33 patients, tumor had metastasized, whereas 21 patients were in remission. FDG PET revealed metastases in 31 patients (sensitivity 93.9%), whereas thyroglobulin levels were elevated in 18 patients (sensitivity 54.5%). FDG PET was positive in 14 of 15 metastatic cancer patients with normal thyroglobulin levels. In 20 of 21 patients in remission, FDG PET was negative (specificity 95.2%), whereas thyroglobulin levels were normal in 16 patients (specificity 76.1%). The sensitivity and specificity of FDG PET were significantly higher than those of serum thyroglobulin. In patients with negative 1311 scans, FDG PET detected cervical lymph node metastasis in 87.9%, lung metastasis in 27.3%, mediastinal metastasis in 33.3% and bone metastasis in 9.1%. In contrast, among 117 patients with 131I scan-positive functional metastases, 131I scan detected cervical lymph node metastasis in 61.5%, lung metastasis in 56.4%, mediastinal metastasis in 22.2% and bone metastasis in 16.2%. In all 5 patients in whom thyroglobulin was false-negative with negative antithyroglobulin antibody, PET showed increased 18F-FDG uptake in cervical lymph nodes, mediastinal lymph nodes, or both. Among patients with increased 18F-FDG uptake only in the cervical lymph nodes, the nodes were dissected in 11. Metastasis was confirmed in all, even in normal-sized lymph nodes. CONCLUSION: FDG PET scan localized metastatic sites in 131I scan-negative thyroid carcinoma patients with high accuracy. In particular, it was superior to 131I whole-body scan and serum thyroglobulin measurement for detecting metastases to cervical lymph nodes. FDG PET was helpful for determining the surgical management of these patients. (+info)
Comparison of dual-head coincidence gamma camera FDG imaging with FDG PET in detection of breast cancer and axillary lymph node metastasis.
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Dual-head coincidence gamma camera 18F-fluorodeoxyglucose (FDG) imaging was compared with FDG PET in the detection of breast cancer and axillary lymph node metastasis. METHODS: Both coincidence gamma camera FDG imaging and FDG PET were performed in a cylindrical phantom containing spheres of different sizes and activity ratios (5:1, 10:1 and 15:1) and in 30 women (age range 32-78 y) with suspected breast cancer. Biopsies or mastectomies were performed in all patients. Images were visually assessed, and the count ratio between tumor and normal tissue (T/N ratio) was calculated. RESULTS: In the phantom studies, coincidence gamma camera imaging visualized the smallest sphere (1.0 cm) at a ratio of 15:1 but not at ratios of 5:1 and 10:1. Coincidence gamma camera imaging visualized the other spheres (> or =1.3 cm) at all ratios. PET visualized all spheres at all ratios. In the clinical studies, 22 of 26 breast carcinomas detected by PET were also detected by coincidence gamma camera imaging.. Coincidence gamma camera imaging detected all of the carcinomas > or =2 cm in diameter (n = 10) and 12 of 16 carcinomas <2 cm. In breast carcinomas detected by both PET and coincidence gamma camera imaging, the T/N ratio in non-attenuation-corrected PET (7.12 +/- 7.13) was significantly higher than in coincidence gamma camera imaging (2.90 +/- 1.47, P < 0.005). Four of 8 axillary lymph node metastases detected by PET were detected by coincidence gamma camera imaging. Of 9 axillary lymph node metastases <1.0 cm in diameter, 7 and 3 were detected by PET and coincidence gamma camera imaging, respectively. CONCLUSION: Coincidence gamma camera imaging is useful in detecting breast carcinoma > or =2 cm in diameter but is not reliable for breast carcinoma <2 cm in diameter. Coincidence gamma camera imaging may be useless or even dangerous in the detection of axillary lymph node metastasis. (+info)
Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study.
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PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease. (+info)