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Collagenous and eosinophilic colitis are rare diseases characterised by chronic watery diarrhoea. Radiographic evaluation of the gastrointestinal tract and colonoscopy are usually non-diagnostic since as many as one-third of patients will have minor abnormalities. To date a few investigators have reported increased fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography (PET) in patients with acute enterocolitis, but there have been no reports on the use of (18)F-FDG PET for the diagnosis of collagenous or eosinophilic colitis in an early clinical stage. The aim of this preliminary study was to evaluate the usefulness of (18)F-FDG PET in the early diagnosis of patients with colitis. We investigated five women (mean age 61.2+/-12.1 years) who had been diagnosed as having colitis in an early clinical stage. In all but one of the patients, the diagnosis of colitis was based on biopsy. Magnetic resonance colonography, ultrasonography and colonoscopy were performed in all but one of the patients. Two women were identified as having collagenous colitis in an early clinical stage. Another two patients had eosinophilic colitis. The morphological imaging methods, magnetic resonance colonography and ultrasonography, yielded no suspicious findings, and the results of colonoscopy similarly showed no abnormalities. One patient had colitis due to bacterial infection. In all patients (18)F-FDG PET showed a pathological increase in tracer uptake in the large bowel, suggestive of colitis. In four of the five patients, colitis was confirmed by histology, and in one, by bacterial analysis. (18)F-FDG PET was able to detect colitis in an early clinical stage, when morphological imaging methods and colonoscopy were non-diagnostic. The early performance of (18)F-FDG PET imaging in patients with possible colitis is encouraging.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:(18)F-FDG positron emission tomography in the early diagnosis of enterocolitis: preliminary results. 1227 24

Increased symmetrical fluorine-18 fluorodeoxyglucose (FDG) uptake in the cervical and thoracic spine region is well known and has been attributed to muscular uptake. The purpose of this study was to re-evaluate this FDG uptake pattern by means of co-registered positron emission tomography (PET) and computed tomography (CT) imaging, which allowed exact localisation of this uptake. Between April and November 2001, 638 consecutive patients referred for PET/CT were imaged on an in-line PET/CT system (GEMS). This system combines an advanced GE PET scanner and a multirow-detector computer tomograph (Lightspeed, GEMS). The examination included PET with FDG and one CT acquisition with 80 mA. For CT, the following parameters were used: 140 kV, 80 mA, reconstructed slice thickness 5 mm, scan length 867 mm, AT 22.5 s. CT data were used for attenuation correction as well as image co-registration. Image analysis was performed on an Entegra work-station (ELGEMS). All patients with symmetrical uptake within the neck, thorax and shoulder regions were selected and the exact localisation of uptake determined (muscle, bone, fatty tissue or articulation). In 17 of the 638 patients (2.5%), increased, symmetrical FDG uptake in the shoulder region in a typical pattern was found. If extensive, this pattern included FDG activity comparable to brain activity in the lower cervical spine, the shoulder region and the upper thoracic spine in the costovertebral region. A less extensive pattern only involved intermediate FDG uptake in the lower cervical spine and shoulder region or in the shoulder region alone. In seven female patients (average 32.3 years), the extensive uptake pattern was seen. The average body mass index (BMI) was 19.0 (range 16.8-23.4). In the other ten patients (two male, eight female, average age 37.1 years), the average BMI was 22.7 (18.7-27.7). In all patients, the soft tissue uptake was clearly localised within the fatty tissue of the shoulders as demonstrated by PET/CT co-registration. The uptake in the region of the thoracic spine was localised in the region of the costovertebral joints. Symmetrical FDG uptake in the shoulder, neck and thoracic spine region is probably related to uptake in adipose tissue, especially in underweight patients. Hypothetically, this FDG uptake could represent activated brown adipose tissue during increased sympathetic nerve system (SNS) activity due to cold stress.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. 1227 25

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.
Eur J Nucl Med Mol Imaging 2002 Dec
PMID:Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects. 1245 94

14( R, S)-[(18)F]Fluoro-6-thia-heptadecanoic acid ([(18)F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [(18)F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [(18)F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [(18)F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [(18)F]FTHA metabolite analysis. Fractional [(18)F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring (18)F in the tissue samples. Fractional [(18)F]FTHA uptake rates based on the analysis of tissue samples were 0.56+/-0.17 ml g(-1) min(-1) and 0.037+/-0.007 ml g(-1) min(-1) for myocardium and skeletal muscle (mean +/- SD), respectively. The myocardial results obtained from the PET data (0.50+/-0.11 ml g(-1) min(-1)) were similar to the values obtained from the tissue samples ( r=0.94, P=0.002). We also found that 89%+/-23% (mean+/-SD, n=7) of the (18)F entered mitochondria in myocardium, as compared with only 36%+/-15% (mean+/-SD, n=7) in skeletal muscle. Intracellular [(18)F]FTHA metabolite analysis showed that a major part of [(18)F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that ~89% of [(18)F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [(18)F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only ~36% of [(18)F]FTHA accumulated in skeletal muscle appears to directly enter mitochondria; the majority is taken up by the other cell fractions, suggesting that in skeletal muscle [(18)F]FTHA traces FFA uptake but not specifically FFA beta-oxidation.
Eur J Nucl Med Mol Imaging 2002 Dec
PMID:14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle. 1245 96

The purpose of this study was to determine the actual standardized uptake value (SUV) by using the lesion size from computer tomography (CT) scan to correct for resolution and partial volume effects in positron emission tomography (PET) imaging. This retrospective study included 47 patients with lung lesions seen on CT scan whose diagnoses were confirmed by biopsy or by follow up CT scan when the PET result was considered negative for malignancy. Each lesion's FDG uptake was quantified by the SUV using two methods: by measuring the maximum voxel SUV (maxSUV) and by using the lesion's size on CT to calculate the actual SUV (corSUV). Among small lesions (2.0 cm or smaller on CT scan), ten were benign and 17 were malignant. The average maxSUV was 1.43+/-0.77 and 3.02+/-1.74 for benign and malignant lesions respectively. When using an SUV of 2.0 as the cutoff to differentiate benignity and malignancy, the sensitivity, specificity, and accuracy were 65%, 70%, and 67% respectively. When an SUV of 2.5 was used for cutoff, the sensitivity, specificity, and accuracy were 47%, 80%, and 59% respectively. The average corSUV was 1.65+/-1.09 and 5.28+/-2.71 for benign and malignant lesions respectively. Whether an SUV of either 2.0 or 2.5 was used for cutoff, the sensitivity, specificity, and accuracy remained 94%, 70%, and 85% respectively. The only malignant lesion that was falsely considered benign with both methods was a bronchioalveolar carcinoma which did not reveal any elevated uptake of fluorine-18 fluorodeoxyglucose (FDG). Of the large lesions (more than 2.0 cm and less than 6.0 cm), one was benign and 19 were malignant and the corSUV technique did not significantly change the accuracy. It is concluded that measuring the SUV by using the CT size to correct for resolution and partial volume effects offers potential value in differentiating malignant from benign lesions in this population. This approach appears to improve the accuracy of FDG-PET for optimal characterization of small lung nodules.
Eur J Nucl Med Mol Imaging 2002 Dec
PMID:Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. 1245 99

Novel 2-(4-aminophenyl)benzothiazoles (e.g., compounds 1 and 2) possess highly selective, potent antitumor properties in vitro and in vivo. Elucidation of the mechanism of action of this structurally simple class of compounds has occurred in parallel with selection of a candidate clinical agent. Antitumor benzothiazoles induce and are biotransformed by cytochrome P 450 1A1 to putative active, as well as inactive metabolites. Metabolic inactivation of the molecule has been thwarted by isosteric replacement of hydrogen with fluorine atoms at positions around the benzothiazole nucleus. Amino acid conjugation to the exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles has been used to overcome limitations posed by drug lipophilicity. Water soluble, chemically stable prodrugs rapidly and quantitatively revert to their parent amine in mice, rats, and dogs in vivo. Plasma concentrations of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (2) regenerated from the lysylamide prodrug (2b), sufficient to elicit cytocidal activity against ZR-75-1 and T47D human mammary carcinoma cell lines persist > 6 h. The growth of breast (MCF-7) and ovarian (IGROV-1) xenograft tumors is significantly retarded by 2b. Manageable toxic side effects are reported from preclinically efficacious doses of 2b. Cytochrome P 450 1A1 protein expression, selectively induced in sensitive carcinoma cells, was detected in MCF-7 and IGROV-1 tumors 24 h after treatment of mice with 2b (20 mg/kg). The lysyl amide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole is potentially suitable for clinical evaluation.
Mol Cancer Ther 2002 Feb
PMID:Preclinical evaluation of amino acid prodrugs of novel antitumor 2-(4-amino-3-methylphenyl)benzothiazoles. 1246 19

Obtaining consistent high image quality is desirable for clinical positron emission tomography (PET). Body morphology may impact image quality. The purpose of this study was to define the average and the range of body sizes in patients undergoing tumor PET studies in our center and to determine how the body habitus affects the statistical and visual quality of PET images. Height, weight, body surface area (BSA), and body mass index (BMI) were determined in 101 male and 101 female patients (group 1) referred for clinical PET. The summed total counts from three consecutive transaxial slices on non-attenuation-corrected (NAC) 2D fluorine-18 fluorodeoxyglucose (FDG) PET images, which included the largest liver section and no lesions, were determined and compared with body morphology and injected doses (ID) in a representative group of 30 male and 30 female patients (group 2) spanning a range of body morphologies. The visual quality of images was also evaluated using a scoring system by three readers. The average height, weight, and BSA were greater in male than in female patients, but the average BMI was not different between them in group 1. The largest value of weight or BMI was more than four times the smallest value in female patients. The total true counts were best correlated with ID/weight (mCi/kg) in group 2 ( r=0.929, P<0.0001). Intermediate to high total counts (930,000 or more) corresponded to ID/weight of 0.22 or higher. The average visual score was positively correlated with the total counts (rho=0.63, P<0.0001) and with ID/weight (rho=0.68, P<0.0001) on NAC images. The image quality in 22 (84.6%) of 26 patients with intermediate to high total counts was adequate to good, whereas that in 21 (61.8%) of 34 patients with lower total counts was suboptimal. A wide variety of body morphologies was observed in patients referred for clinical FDG-PET tumor studies in our center. The total counts and average image visual score were negatively correlated with weight. Counts in heavy patients were as low as one-fourth those in light patients. Adjusting injected FDG dose in each patient on the basis of body weight may be more appropriate to achieve consistent PET image quality than giving a fixed injected FDG dose.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Impact of body habitus on quantitative and qualitative image quality in whole-body FDG-PET. 1248 8

The aim of this study was to evaluate the possible usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting tumour aggressiveness and response to intra-arterial chemotherapy (THP-ADM + 5-FU + carboplatin) and radiotherapy in head and neck carcinomas. Twenty patients with squamous cell carcinoma (SCC) of the head and neck were included in the study. All patients completed the treatment regimen, and each patient underwent two FDG-PET studies, one prior to and one at 4 weeks after the chemoradiotherapy. For the quantitative evaluation of regional FDG uptake in the tumour, standardised uptake values (SUVs) with an uptake period of 50 min were used. The pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV) were compared with immunohistologically evaluated tumour proliferative potential (MIB-1 and PCNA), tumour cellularity and other parameters including histological grade, tumour size and stage, clinical response and histological evaluation after therapy. All neoplastic lesions showed high SUVs (mean, 9.75 mg/ml) prior to the treatment, which decreased significantly after the therapy (3.41 mg/ml, P<0.01). Pre-SUV did not show any correlation with MIB-1, PCNA, cellularity or other parameters. However, lower post-SUV was significantly correlated with good histological results after therapy (no viable tumour cells, n=16). In comparison with moderately differentiated SCCs, well-differentiated SCCs exhibited significantly lower post-SUV and a larger difference between pre- and post-SUVs. Lesions with a high pre-SUV (>7 mg/ml) showed residual tumour cells after treatment in 4 out of 15 patients, whereas patients whose lesions showed a low pre-SUV (<7 mg/ml, five patients) were successfully treated. Four out of six tumours with a post-SUV higher than 4 mg/ml had viable tumour cells, whereas all tumours (14/14) with a post-SUV lower than 4 mg/ml showed no viable tumour cells. Computational multivariate analysis using multiple regression revealed four factors (MIB-1 labelling index, cellularity, the number of MIB-1 labelled tumour cells and tumour size grade) contributing to pre-SUV and pre-post SUV (difference between pre-treatment SUV and post-treatment SUV in each patient) with statistical significance. FDG uptake in the tumour might reflect tumour aggressiveness, which is closely related to the proliferative activity and cellularity. Pre-treatment FDG-PET is useful in predicting the response to treatment, and post-treatment FDG-PET is of value in predicting residual viable tumours. FDG-PET has a profound impact on the treatment strategy for head and neck carcinomas.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:FDG-PET for prediction of tumour aggressiveness and response to intra-arterial chemotherapy and radiotherapy in head and neck cancer. 1248 11

Positron emission tomography (PET) utilizing fluorine-18 fluorodeoxyglucose (FDG) has been used in the evaluation of non-small cell lung cancer (NSCLC). Recently its use in the staging of small cell lung cancer (SCLC) has been reported. However, the prognostic value of FDG-PET imaging in SCLC has not been studied. We performed a retrospective analysis to assess this, with the following hypotheses: (1) PET-positive patients would have a less favorable prognosis than PET-negative patients and (2) a high standardized uptake value (SUV) would be associated with a poor prognosis. Retrospective review of a mixed population of treated and untreated patients imaged between 1995 and 2000 was performed. Results of 62 scans in 46 patients were analyzed. There were 8 untreated and 38 treated patients. Findings were correlated with pathology, computed tomography/magnetic resonance imaging and clinical data. The sensitivity of PET scanning was 100% with pathological correlation. The prognostic value of a positive PET study was determined. Overall survival in PET-positive cases was significantly worse than that in PET-negative cases ( P=0.0108). Correlation of SUV(max) with survival showed a significant negative correlation ( P=0.0021). In the eight untreated patients, scans were strongly positive and in all cases the scan results concurred with the final clinical stage assigned on the basis of conventional methods. We conclude that FDG-PET imaging provides prognostic information in treated patients. A positive study and a high SUV(max) are significantly associated with poor survival. Additionally, FDG-PET may be helpful in staging and follow-up.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Prognostic value of [18F]FDG-PET imaging in small cell lung cancer. 1248 13

Fluorine-18 fluoroerythronitroimidazole ([(18)F]FETNIM) is a nitroimidazole compound that is potentially useful as a hypoxia marker in positron emission tomography (PET) studies of oncological patients. Our aim was to develop a simple protocol to quantitate uptake of [(18)F]FETNIM in hypoxic tumours. Dynamic imaging data from ten patients with head and neck cancer undergoing [(18)F]FETNIM PET was used in simulations and model fits to assess hypoxia marker uptake under different levels of blood flow. The distribution volume determined from dynamic PET study was compared with simple tumour to plasma and tumour to muscle ratios at 90-120 min. In skeletal muscle having a low but variable blood flow [2-6 ml/(100 gxmin)], differences in hypoxia-specific uptake of [(18)F]FETNIM remain small and may be hard to detect with PET. At higher blood flow [>20 ml/(100 gxmin)], the retention of [(18)F]FETNIM reflects the oxygenation status well and results in satisfactory contrast between hypoxic and well-oxygenated tissue. A good estimate of tissue hypoxia is accomplished by measuring the tissue to plasma [(18)F]FETNIM activity ratio using only a few late time points. The increased hypoxia-specific retention of [(18)F]FETNIM in tissues with high blood flow, such as malignant tumours, may facilitate application of [(18)F]FETNIM as a hypoxia marker in oncological patients. In the assessment of the tumour to non-target uptake ratio, plasma is the preferred reference tissue rather than muscle, which may show a more heterogeneous tracer uptake not easily controlled for.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio. 1248 16


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