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Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET. 1192 85

The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (FDG PET) for the non-invasive differentiation of focal pancreatic lesions originating from cancer or chronic pancreatitis by combined visual image interpretation and semiquantitative uptake value analysis has been documented. However, in clinical routine some misdiagnosis is still observed. This is because there is potential overlap between the semiquantitative uptake values obtained for active inflammatory lesions and cancer. Therefore, this prospective study was undertaken to test the hypothesis that analysis of dynamic kinetics of focal pancreatic lesions based on FDG PET may more accurately determine the benign or malignant nature of such lesions. Thirty patients (56+/-17 years) were studied dynamically with FDG PET for a period of 60-90 min. Patients were assigned to one of four groups: control, acute pancreatitis, chronic pancreatitis or pancreatic cancer. Two observers, blinded to the clinical data, analysed the time-activity curves of FDG kinetics based on region of interest analysis. The diagnosis predicted by FDG PET was compared with the result of histological examination of the surgical specimen. Analysis of FDG kinetics revealed significant differences in the shape of the time-activity curve for controls, pancreatic cancer and inflammatory disease. Surprisingly, there was no significant difference in the time-activity curve shape for chronic pancreatitis and acute pancreatitis; this is, however, not a clinical issue. Furthermore, acquisition time (60 min vs 90 min) did not affect interpretation of the time-activity curve, so that scanning time may be regularly shortened to 60 min. Interobserver agreement was 1. Based on these findings, non-invasive differentiation between pancreatic cancer and chronic pancreatitis was correctly predicted in all cases, as confirmed by histology. In addition, the specificity was increased compared with that obtained from standardised uptake value analysis. Non-invasive differentiation between pancreatic cancer and chronic pancreatitis may best be achieved based on a dynamic FDG PET study including kinetic analysis. This approach yields results superior to those obtained from a semiquantitative analysis of pancreatic lesions.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:Non-invasive differentiation of pancreatic lesions: is analysis of FDG kinetics superior to semiquantitative uptake value analysis? 1192 86

The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc(real)). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc(sim)) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC(real)) and simulated input function (AUC(IFsim)) and percent error between CMRGlc(real) and CMRGlc(sim) were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165+/-69 vs 100+/-9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%+/-1.3% vs 3.5%+/-2.2% in AUC, P=0.0015; 18.2%+/-2.2% vs 2.9%+/-1.9% in CMRGlc in grey matter, P=0.0028; 24.0%+/-4.6% vs 3.4%+/-2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects. 1192 88

The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake by recurrences or metastases of differentiated thyroid carcinomas has not yet been clarified. The aim of this study was to ascertain whether the administration of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions. In this prospective study, 30 patients with positive or equivocal thyroglobulin (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET) under exogenous TSH suppression and under exogenous TSH stimulation of serum levels by injection of rhTSH. The mean interval between the FDG-PET studies under these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid hormones were determined on each occasion. FDG uptake was quantitated using tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like lesions). The total number of foci was 45. After exogenous TSH stimulation, the number of patients in whom FDG foci were detected was 19, and the number of foci identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus 2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory lymph nodes, TBR and SUV were only marginally increased under TSH stimulation (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ significantly from those obtained under suppression. These results provide the first direct evidence that TSH stimulates FDG uptake by differentiated thyroid carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under suppression.
Eur J Nucl Med Mol Imaging 2002 May
PMID:Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma. 1197 2

Sampling of arterialised venous blood (AVB) is often used as an alternative to sampling of arterial blood when determining the myocardial metabolic rate of glucose (MRGlu). This method, however, has not yet been validated for measurement of plasma fluorine-18 fluorodeoxyglucose (FDG) activity during a euglycaemic-hyperinsulinaemic clamp (EHC). In this study, dynamic FDG scans were performed with arterial blood sampling during EHC. Samples of arterial and AVB or venous blood were simultaneously withdrawn at five time points for measurement of FDG activity and plasma glucose in 36 patients. Both venous to arterial and AVB to arterial ratios were calculated for FDG activity and plasma glucose. Mean ratios between AVB and arterial FDG activity were then used to create calculated arterialised venous input functions from corresponding arterial input functions. The mean effect of arterialisation on the calculation of K(i) was assessed. In nine additional patients, K(i) obtained with continuous sampling of AVB was compared with K(i) obtained with a corresponding (quality-controlled) image-derived input function from the ascending aorta. Using AVB, measurements of FDG activity were much more reliable than with venous blood sampling. As compared with arterial sampling, however, FDG activity was underestimated early after injection, while it was overestimated after 20 min. In both analyses, AVB resulted in approximately 10%+/-10% overestimation of K(i). Because of a 5%+/-5% underestimation of plasma glucose concentration with AVB, the net effect on the final calculation of MRGlu was small (on average 5% overestimation). It is concluded that the use of AVB has a small average effect on the determination of MRGlu. This method does, however, contribute to variability in the results. This variability cannot be explained by different degrees of arterialisation.
Eur J Nucl Med Mol Imaging 2002 May
PMID:Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping. 1197 5

The currently preferred radiopharmaceutical for positron emission tomography (PET) in oncology is 2-[(18)F]fluoro-deoxyglucose (FDG). Increased accumulation of this deoxyglucose analogue in tumour cells is based on elevated glucose metabolism by tumour cells and subsequent trapping in the cells. In the search for new PET tracers, amino acids have been widely studied. A new amino acid tracer should preferably have similar high uptake in tumour cells but low non-specific uptake in normal tissues and any pathology other than tumour. In recent years, several amino acids have been labelled with either gamma radiation-emitting radionuclides or positron-emitting radionuclides, the most commonly used being carbon-11. However, the longer half-life of fluorine-18 matches better with the relatively slow process of protein synthesis and also facilitates shipping of the radiolabelled amino acids to hospitals without an on-site cyclotron or dedicated radiochemistry laboratory. The number of fluorinated amino acids under investigation is increasing, and one of the major points of discussion is the underlying mechanism of the tumour visualisation. While it has been shown that some amino acids can be used to measure the protein synthesis rate, others are used with the sole aim of measuring the rate of uptake into the cell. The differences between measuring amino acid transport (rate) and protein synthesis rate with (18)F-labelled amino acids are discussed.
Eur J Nucl Med Mol Imaging 2002 May
PMID:Fluorinated amino acids for tumour imaging with positron emission tomography. 1197 9

In this study we evaluated on-line continuous blood sampling in a femoral arteriovenous (a-v) shunt for use in quantitative tracer studies using gamma-emitting radionuclides in animals. The shunt consisted of 40 cm polyethylene tubing (PE-50) guided through a coincidence probe. Two three-way valves allowed blood pressure measurements and tracer injection. Blood flow in the shunt and the impulse response function (IRF) were assessed using heparinized human blood mixed with fluorine-18 fluorodeoxyglucose (FDG). In vivo experiments were performed in eight male rats (300-350 g) anaesthetized with halothane. In three rats, manual blood sampling was performed in parallel with on-line sampling. In another five animals, the arterial whole blood activity was recorded on-line for 40 min. For the experiments 150-180 MBq FDG was injected over 35 s. Blood flow in the shunt was 23.6, 29.2 and 42.8 ml/h at 100, 120 and 160 mmHg, respectively. The IRF was characterized by minimal dispersion (1-2 s FWHM). Deconvolution of the measured arterial input curves with the IRF changed the measured curve only minimally. Whole blood radioactivity concentration derived from manual and on-line sampling were in excellent agreement. The curves derived from on-line sampling were of high statistical quality. In conclusion, a femoral a-v shunt allows multiple manipulations such as measurement of the arterial whole blood activity, continuous blood pressure monitoring, injection of the tracer and collection of blood samples if necessary. It is not associated with blood loss if the collection of blood samples is not required. It is more convenient to use than manual sampling, the peak of the input curve is never missed and the input curves are of high statistical quality.
Eur J Nucl Med Mol Imaging 2002 Mar
PMID:A femoral arteriovenous shunt facilitates arterial whole blood sampling in animals. 1200 5

While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is only available in selected centres. Therefore, single-photon emission tomography (SPET) tracers would be desirable if they were to demonstrate tumour uptake reliably. This multitracer study was performed to evaluate the pretherapeutic uptake of the SPET tracers iodine-123 alpha-methyl-L-tyrosine (IMT) and technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) in primary carcinomas of the hypopharynx and larynx and to compare the results with those of FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5+/-10.2 years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was acquired after intravenous injection of 232+/-43 MBq 18F-FDG. Data analysis was semiquantitative, being based on standardised uptake values (SUVs) obtained at 60-90 min after injection. After injection of 570+/-44 MBq 99mTc-MIBI, cervical SPET scans (high-resolution collimator, 64x64 matrix, 64 steps, 40 s each) were obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min after injection of 327+/-93 MBq 123I-IMT (medium-energy collimator, 64x64 matrix, 64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of 8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in 13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13 of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to muscle ratio of 2.2 and no significant difference between early and late MIBI SPET images (P=0.23). In conclusion, in the diagnosis of primary carcinomas of the hypopharynx and larynx, IMT SPET achieved a detection rate comparable to that of FDG PET. IMT SPET was clearly superior to MIBI SPET in this population. A further evaluation of the specificity of IMT in a larger number of patients appears justified.
Eur J Nucl Med Mol Imaging 2002 Mar
PMID:Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F-fluorodeoxyglucose, 123I-alpha-methyl-L-tyrosine and 99mTc-hexakis-2-methoxyisobutylisonitrile. 1200 6

Because anatomical information on fluorine-18 fluorodeoxyglucose (FDG) whole-body positron emission tomography (PET) images is limited, combination with structural imaging is often important. In principle, software co-registration of PET and computed tomography (CT) data or dual-modality imaging using a combined PET-CT camera has an important role to play, since "hardware-co-registered" images are thereby made available. A major unanswered question is under which breathing protocol the respiration level in the CT images of a patient will best match the PET images, which represent summed images over many breathing cycles. To address this issue, 28 tumour patients undergoing routine FDG PET examinations were included in this study. In ten patients, PET and CT were performed using a new combined high-performance in-line PET-CT camera without the need for repositioning of the patient, while in 18 patients imaging was performed on separate scanners located close to each other. CT was performed at four respiration levels: free breathing (FB), maximal inspiration (MaxInsp), maximal expiration (MaxExp) and normal expiration (NormExp). The following distances were measured: (a) between a reference point taken to be the anterior superior edge of intervertebral disc space T10-11 and the apex of the lung, (b) from the apex of the lung to the top of the diaphragm, (c) from the apex of the lung to the costo-diaphragmatic recess and (d) from the reference point to the lateral thoracic wall. Differences between CT and corresponding PET images in respect of these distances were compared. In addition, for each of 15 lung tumours in 12 patients, changes in tumour position between PET and CT using the same protocol were measured. CT during NormExp showed the best fit with PET, followed by CT during FB. The mean differences in movement of the diaphragmatic dome on CT during NormExp, FB, MaxInsp and MaxExp, as compared with its level on PET scan, were, respectively, 0.4 mm (SD 11.7), -11.6 mm (13.3), -44.4 mm (25.5) and -9.5 mm (25.6). CT acquired in MaxExp and MaxInsp is not suitable for image co-registration owing to the poor match of images in MaxInsp and because of difficulties with patient performance in MaxExp. With reference to lung lesions, NormExp showed the best results, with a higher probability of a good match and a smaller range of measured values in comparison with FB. Image misregistration in combined PET-CT imaging can be minimized to dimensions comparable to the spatial resolution of modern PET scanners. For PET-CT image co-registration, the use of a normal expiration breath-hold protocol for CT acquisition is recommended, independent of whether combined PET-CT systems or stand-alone systems are used.
Eur J Nucl Med Mol Imaging 2002 Mar
PMID:PET-CT image co-registration in the thorax: influence of respiration. 1200 10

This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.
Eur J Nucl Med Mol Imaging 2002 Mar
PMID:Initial results in the assessment of multiple myeloma using 18F-FDG PET. 1200 11


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