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Fever of unknown origin (FUO) and suspected focal infection or inflammation are challenging medical problems. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with FUO and patients with suspected focal infection or inflammation. All FDG PET scans ordered because of FUO or suspected focal infection or inflammation in the last 4 years were reviewed. These results were compared with the final diagnosis. Thirty-five FDG PET scans were performed in 35 patients with FUO. A final diagnosis was established in 19 patients (54%). Of the total number of scans, 37% were clinically helpful. The positive predictive value of FDG PET in these patients was 87% and the negative predictive value was 95%. Fifty-five FDG PET scans were performed in 48 patients with suspected focal infection or inflammation. A final diagnosis was established in 38 patients (82%). Of the total number of scans, 65% were clinically helpful. The positive predictive value of FDG PET in these 55 episodes of suspected infection or inflammation was 95% and the negative predictive value was 100%. It is concluded that FDG PET appears to be a valuable imaging technique in the evaluation of FUO and suspected focal infection or inflammation. Furthermore, FDG PET could become a useful tool for evaluating the effect of treatment of infectious and inflammatory processes that cannot reliably be visualised by conventional techniques. However, to assess the additional diagnostic value of this technique, prospective studies of FDG PET as part of a structured diagnostic protocol are warranted.
Eur J Nucl Med Mol Imaging 2004 Jan
PMID:Clinical value of FDG PET in patients with fever of unknown origin and patients suspected of focal infection or inflammation. 1455 52

This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1-2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1-2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24-34 months) while the other six have relapsed (PFS 8-16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1-2 cycles of therapy as compared with the non-responders (81.2%+/-9.5% vs 35.0%+/-20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.
Eur J Nucl Med Mol Imaging 2004 Jan
PMID:Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and Hodgkin's lymphoma. 1457 14

This article reviews the literature on the use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and thallium-201, technetium-99m sestamibi and technetium-99m tetrofosmin single-photon emission tomography (SPET) for the diagnosis and staging of primary and recurrent squamous cell carcinoma of the head and neck (SCCHN). A search of the MEDLINE and CancerLit databases covering articles entered between 1989 and February 2003 was performed. In the case of FDG PET, only full-ring PET studies that included comparison with conventional morphological imaging were considered. Due to the wide variation in methodology, a straightforward meta-analysis of FDG PET literature was impossible. Instead, indicative summary receiver-operating curves of FDG PET and morphological imaging techniques were generated and a paired comparison of the sensitivities and specificities of FDG PET and morphological imaging performed. Compared with conventional morphological imaging, FDG PET proved as sensitive and specific for the detection of primary SCCHN but more sensitive and specific for the detection of cervical lymph node involvement (CLNI) and recurrence of SCCHN. Additional studies addressing the role of FDG PET in screening for distant metastases and synchronous primary tumours are mandatory. Following negative conventional evaluations, FDG PET identifies occult primary tumours in 20-50% of patients presenting with CLNI. As regards the use of 201Tl, 99mTc-sestamibi and 99mTc-tetrofosmin, more studies are required to define whether these imaging agents could form part of the current diagnostic armamentarium in SCCHN patients. It is concluded that FDG PET either is superior to or offers added value when compared with conventional morphological imaging techniques for the purpose of diagnosis and staging of primary and recurrent SCCHN.
Eur J Nucl Med Mol Imaging 2003 Dec
PMID:Nuclear medicine imaging for the assessment of primary and recurrent head and neck carcinoma using routinely available tracers. 1457 16

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between <euro>736 and <euro>1,588 depending on the (hospital) setting and the procurement of (18)FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile ( P=0.003). The average costs per patient in the CWU group were <euro>9,573 and in the PET group, <euro>8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective.
Eur J Nucl Med Mol Imaging 2003 Nov
PMID:Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study. 1457 81

Iterative reconstruction algorithms, such as the ordered subsets expectation maximisation (OS-EM), are a promising alternative to filtered backprojection (FBP). The aims of this study were first to optimise the OS-EM algorithm in terms of iteration number and to study the usefulness of post-filtering, and second to compare OS-EM and FBP for image reconstruction on a fluorine-18 fluorodeoxyglucose ((18)F-FDG) dual-head camera (DHC). These two goals were addressed using phantom acquisitions. The performances of these algorithms were also studied in patient acquisitions performed on a DHC and a PET on the same day. Phantom experiments were performed on a DHC using a Jaszczak phantom containing six spheres filled with (18)F-FDG, two background levels (0.95, 6.80 kBq/ml) and three object contrasts (5.9, 3.7, 2.7). The reconstruction algorithms were FBP with a Gaussian filter (FWHM 0.5-2 pixel width) and OS-EM using 8-128 equivalent iterations (equivalent to the ML-EM algorithm) with and without Gaussian post-filtering [OS-EM (iterations, pixel width)]. Contrast recovery coefficient (CRC) and noise characteristics were assessed. Twenty-two patients (21 male, one female; age 55+/-15 years) with lung cancer underwent, on the same day, PET (1 h post injection of 37 MBq/kg (18)F-FDG) and DHC acquisitions (3 h post injection). DHC data were reconstructed using six methods: FBP (1), OS-EM (16), (40), (40,1), (64) and (64,1). These sets were evaluated by two observers and compared to PET reconstructed with OS-EM (16). The number of detected lesions and the visual quality were assessed. A marked improvement in CRC was observed with OS-EM as compared with FBP when more than 24 iterations were used. The CRC increased markedly from 8 to 40 iterations and then reached a plateau. The noise was stable until 40 iterations and then increased. The best compromise was obtained for OS-EM (32) and OS-EM (40,1). For the patient study, OS-EM provided images of better visual quality, but with no significant difference in detection sensitivity. OS-EM was superior to FBP in terms of contrast recovery and noise level. The optimal compromise between contrast recovery and noise was obtained for OS-EM (32) and (40,1) on the phantom study. The clinical study showed that OS-EM yielded images of better visual quality but with no improvement in terms of detection of lung cancer.
Eur J Nucl Med Mol Imaging 2003 Nov
PMID:Optimisation of the OS-EM algorithm and comparison with FBP for image reconstruction on a dual-head camera: a phantom and a clinical 18F-FDG study. 1457 91

Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22-90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A ( n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B ( n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive (99m)Tc-TOC findings was positively correlated ( P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with (18)F-FDG PET ( P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohen's kappa of 0.62 (0.47-0.78)]. In conclusion, scintigraphy with (99m)Tc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.
Eur J Nucl Med Mol Imaging 2004 Mar
PMID:99mTc-EDDA/HYNIC-TOC and (18)F-FDG in thyroid cancer patients with negative (131)I whole-body scans. 1462 64

The detection of hibernating myocardium is important because revascularisation results in improved function and prognosis in patients with hibernation but not in those with non-viable myocardium. The primary aim of this study was to compare the diagnostic accuracy of four techniques with respect to hibernation in the same study population with 6-12 months of follow-up. Twenty-five males underwent rest-stress sestamibi and delayed (>18 h) thallium scintigraphy, high-dose dobutamine stress echocardiography and nitrogen-13 ammonia/fluorine-18 fluorodeoxyglucose (NH(3)/FDG) positron emission tomography (PET). The pre-operative ejection fraction was 36.2% (+/-7.3%). Follow-up was 8.1 (+/-2.8) months. Using postoperative improvement in wall motion on echocardiography as the gold standard, 6/34 dysfunctional vascular territories were hibernating. The mean uptake of all tracers was significantly higher in hibernating than in non-viable territories ( P<0.05). Normal perfusion or mismatch on PET (FDG>NH(3) uptake) and the pattern of response to dobutamine on echocardiography were also predictive of recovery ( P<0.001 and P=0.02 respectively). Univariate logistic regression identified sestamibi, ammonia and FDG as independent predictors of hibernation. FDG-PET was, however, the only independent predictor using multivariate analysis. The nuclear techniques had high negative predictive values (NPV) of >or=95% but lower positive predictive values (PPV) of 45%-75% as compared with echocardiography, which had an NPV of 87% and a PPV of 100%. PET was the most powerful predictor of hibernation although the combination of a technique with a high PPV (echocardiography) and a high NPV (PET or sestamibi) may represent the optimal clinical choice.
Eur J Nucl Med Mol Imaging 2004 Mar
PMID:Comparison of sestamibi, thallium, echocardiography and PET for the detection of hibernating myocardium. 1519 6

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone ( P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.
Eur J Nucl Med Mol Imaging 2004 Mar
PMID:FDG-PET/CT in re-staging of patients with lymphoma. 1464 88

We measured neutrophil glucose uptake with positron emission tomographic imaging and [18F]fluorodeoxyglucose ([18F]FDG-PET) in anesthetized dogs after intravenous oleic acid-induced acute lung injury (ALI; OA group, n = 6) or after low-dose intravenous endotoxin (known to activate neutrophils without causing lung injury) followed by OA (Etx + OA group, n = 7). The following two other groups were studied as controls: one that received no intervention (n = 5) and a group treated with Etx only (n = 6). PET imaging was performed 1.5 h after initiating experimental interventions. The rate of [3H]deoxyglucose ([3H]DG) uptake was also measured in vitro in cells recovered from bronchoalveolar lavage (BAL) performed after PET imaging. Circulating neutrophil counts fell significantly in animals treated with Etx but not in the other two groups. The rate of [18F]FDG uptake, measured by the influx constant Ki, was significantly elevated (P < 0.05) in both Etx-treated groups (7.9 +/- 2.6 x 10(-3) ml blood x ml lung(-1) x min(-1) in the Etx group, 9.3 +/- 4.8 x 10(-3) ml blood x ml lung(-1) x min(-1) in the Etx + OA group) but not in the group treated only with OA (3.4 +/- 0.8 x 10-3 ml blood x ml lung(-1) x min(-1)) when compared with the normal control (1.6 +/- 0.4 x 10(-3) ml blood x ml lung(-1) x min(-1)). [3H]DG uptake was increased (73 +/- 7%) in BAL neutrophils recovered from the Etx + OA group (P < 0.05) but not in the OA group. Ki and [3H]DG uptake rates were linearly correlated (R2 = 0.65). We conclude that the rate of [18F]FDG uptake in the lungs during ALI reflects the state of neutrophil activation. [18F]FDG-PET imaging can detect pulmonary sequestration of activated neutrophils, despite the absence of alveolar neutrophilia. Thus [18F]FDG-PET imaging may be a useful tool to study neutrophil kinetics during ALI.
Am J Physiol Lung Cell Mol Physiol 2004 Apr
PMID:Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. 1466 Apr 87

Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 micro U/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of TSH.
Eur J Nucl Med Mol Imaging 2004 Apr
PMID:Influence of TSH on uptake of [18F]fluorodeoxyglucose in human thyroid cells in vitro. 1472 74


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