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The aim of this study was to assess the usefulness of fluorine-18 fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) in the post-therapy surveillance of endometrial carcinomas. Forty-one fully corrected whole-body PET studies were performed in 34 women with previously treated endometrial cancers as a part of their follow-up programme. In 28 studies, FDG PET was indicated to localise a recurrence suspected at the control visits on the basis of clinical examination and/or radiological abnormalities (chest X-ray, CT or MRI) and/or elevated tumour marker levels (CA125, CEA). Another 13 studies were performed as a simple surveillance procedure. Overall, in 26 studies PET detected recurrent disease, which was confirmed either by histology ( n=7) or by clinical and radiological outcomes ( n=19). In 88% of the cases, the PET findings confirmed recurrence suggested by routine follow-up. In the remaining 12% of cases, PET detected asymptomatic recurrences that were unsuspected at the control visits. Whole-body PET accurately localised the site of confirmed recurrences as being above and below the diaphragm in 50%, only below the diaphragm in 35% and only above the diaphragm in 15%. In one patient, however, PET missed microscopic lung metastases shown on thoracic CT, and in three studies, metabolic imaging results were not confirmed. In 11 of 12 negative PET studies, no subsequent clinical or radiological recurrences were observed with a median follow-up of 10 months. Overall, the results of PET agreed well with the final diagnosis (Cohen's kappa coefficient =0.78). In 9/26 patients (35%) with confirmed recurrences, the PET findings significantly altered the treatment choice by detecting either clinically or radiologically unsuspected distant metastases. The sensitivity, specificity, diagnostic accuracy and positive and negative predictive values of FDG PET imaging in the post-therapy surveillance of endometrial carcinomas were 96%, 78%, 90%, 89% and 91%, respectively. Indeed, the high likelihood ratio for a positive test result (4.5) and the low likelihood ratio for a negative test result (0.05) demonstrated the clinical utility of metabolic imaging in "ruling in" disease as well as "ruling out" recurrence. In conclusion, whole-body FDG PET appears useful in the post-therapy surveillance of endometrial cancers, both for the accurate localisation of suspected recurrences and for the detection of asymptomatic recurrent disease.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:Usefulness of (18)F-FDG PET in the post-therapy surveillance of endometrial carcinoma. 1219 57

In a retrospective analysis of patients with sarcoma who underwent fluorodeoxyglucose positron emission tomography (FDG PET) imaging, tumor maximum FDG uptake was analyzed for ability to predict patient survival and disease-free interval. Two hundred and nine patients with sarcoma were imaged prior to treatment with neoadjuvant chemotherapy or resection. Tumor FDG uptake expressed as maximum standard uptake value (SUV(max)) was compared with disease-free and overall survival. A multivariate Cox regression analysis was applied to examine the role of SUV(max) in predicting time to death or disease progression, after adjusting for standard clinical prognostic factors. The multivariate analyses showed that the SUV(max) information is a statistically significant independent predictor of patient survival. Tumors with larger SUV(max) have a significantly poorer prognosis. This retrospective analysis indicates that the sarcoma tumor SUV(max) value determined by PET is an independent predictor of survival and disease progression.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis. 1219 59

While characterization of lung lesions and staging of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is an established clinical procedure, a lower diagnostic accuracy of FDG-PET for diagnosis and staging of so-called bronchioloalveolar carcinoma (BAC) has been reported. Therefore, the accuracy of PET for diagnosing and staging of BAC was investigated. We studied 41 patients eventually found to have adenocarcinoma with a bronchioloalveolar growth pattern who were referred for characterization or staging of lung lesions with whole-body FDG-PET between January 1998 and March 2001: there were 11 males (27%) and 30 females (73%), with a mean age of 66.0+/-10.9 (range =44-84 years). Patients were imaged using ECAT EXACT or HR+ systems. All patients had non-attenuation-corrected scans, while transmission data for attenuation correction were also available for 12 patients (29%). PET correctly identified BAC in 41 of the 46 (89%) lesions and 39 of the 41 patients (95%). By pathology, 25 patients (61%) were found to have unifocal or nodular lesions; this pattern was correctly identified by PET in 20 patients (80%) and by CT in 18 (72%). PET correctly identified 7 (44%) of 16 patients (39%) who had multicentric or diffuse BAC, and CT identified 11 (69%). Of the 35 patients whose lymph node status was verified pathologically, PET was correct in 27 (77%) and CT in 24 (69%). PET missed 67% of the rare tumors that had a pure BAC pattern with no invasive component. It is concluded that the diagnostic performance of whole-body FDG-PET is similar in most patients with lesions with a BAC pattern and in other non-small cell lung cancer types. PET is less accurate in patients with rare BAC tumors that have no invasive component.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar carcinoma? 1219 61

Here we report the expression of major pyrimidine metabolising enzymes in pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic cancer and the in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT). The expression of pyrimidine metabolising enzymes was evaluated with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1) activity was measured with a fluorocytometric assay. The cellular uptake and intracellular metabolism of [(18)F]FLT were evaluated in pancreatic lobules and in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were increased in six pancreatic cancer cell lines, while mRNA levels of thymidine kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human pancreatic cancer as compared with normal pancreatic tissue and samples from patients with chronic pancreatitis. The cellular uptake of [(18)F]FLT was 18.4%+/-3.6% and 5.2%+/-1.4% of the applied radioactivity after 240 min in SW-979 and BxPc-3 cells, respectively, while uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) was only 0.6%+/-0.04% (SW-979) and 0.3%+/-0.13% (BxPc-3) after 240 min of incubation. In contrast, cellular uptake of [(18)F]FLT in isolated pancreatic lobules and growth-arrested HT1080 cells was lower as compared with the uptake of [(18)F]FDG and with the malignant pancreatic cancer cell lines. HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the phosphorylation of [(18)F]FLT to the respective monophosphate in both cell lines. Furthermore, 0.8%+/-0.12% (BxPc-3) and 1.3%+/-0.38% (SW-979) of the applied radioactivity was detected in the perchloric acid-insoluble cell fraction, indicating the incorporation of [(18)F]FLT into the DNA. Our results demonstrate the cellular uptake, intracellular trapping and incorporation into the DNA of [(18)F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme of [(18)F]FLT metabolism, is overexpressed in pancreatic cancer cell lines and in human pancreatic cancer. Thus, we propose [(18)F]FLT as a promising tracer for positron emission tomography that might overcome current limitations in the diagnosis of pancreatic cancer.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines. 1219 62

The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c- erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6-122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4-22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%+/-13.8% (median 10%, range 0%-60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer ( P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c- erb B2 ( P=0.79), p53 ( P=0.92), tumour grading ( P=0.09), oestrogen receptor status ( P=0.41), progesterone receptor status ( P=0.34), axillary lymph node status ( P=0.90) and tumour size ( P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer ( P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining ( P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. 1227 13

Hip arthroplasty is a common surgical procedure, but the diagnosis of infection associated with hip arthroplasty remains challenging. Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been shown to be a promising imaging modality in settings where infection is suspected. However, inflammatory reaction to surgery can result in increased FDG uptake at various anatomic locations, which may erroneously be interpreted as sites of infection. The purpose of this study was to assess the patterns and time course of FDG accumulation following total hip replacement over an extended period of time. Firstly, in a prospective study nine patients with total hip replacement were investigated to determine the patterns of FDG uptake over time. Three FDG-PET scans were performed in each patient at about 3, 6 and 12 months post arthroplasty. Secondly, in a retrospective analysis, the medical and surgical history and FDG-PET imaging results of 710 patients who had undergone whole-body scans for the evaluation of possible malignant disorders were reviewed. The history of arthroplasty and FDG-PET findings in the hip region were reviewed for this study. Patients with symptomatic arthroplasties or related complaints during FDG-PET scanning were excluded from the analysis. During the entire study period, all nine patients enrolled in the prospective study were demonstrated to have increased FDG uptake around the femoral head or neck portion of the prosthesis that extended to the soft tissues surrounding the femur. Among the patients reviewed in the retrospective study, 18 patients with a history of 21 hip arthroplasties who were asymptomatic at the time of FDG-PET scan met the criteria for inclusion. The time interval between the hip arthroplasty and the FDG-PET study ranged from 3 months to 288 months (mean+/-SD: 80.4+/-86.2 months). In 81% (17 of 21) of these prostheses, increased FDG uptake could be noted around the femoral head or neck portion of the prosthesis. The average time interval between arthroplasty and FDG-PET scan in these patients was 71.3 months. In only four prostheses (19%, 4 of 21) was no abnormally increased FDG uptake seen around the prostheses or adjacent sites. The average time interval in these patients was 114.8 months. It is concluded that following hip arthroplasty, non-specifically increased FDG uptake around the head or neck of the prosthesis persists for many years, even in patients without any complications. Therefore, to minimize the number of false-positive results for infection with PET studies obtained to evaluate a painful hip prosthesis, caution should be exercised when interpreting FDG uptake around the head or neck portion of the prosthesis.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:Persistent non-specific FDG uptake on PET imaging following hip arthroplasty. 1227 15

Fluorine-18 fluoro-2-deoxyglucose ((18)FDG) and carbon-14 2-deoxyglucose ((14)C-2-DG) are both widely used tracers of myocardial glucose uptake and phosphorylation. We have recently shown, using positron emission tomography (PET) and nuclear magnetic resonance, that ischaemia-reperfusion (I-R) causes differential changes in their uptake. We describe here the novel application of an autoradiographic technique allowing the investigation of this phenomenon at high resolution, using tracer concentrations of both analogues in the dual-perfused isolated rat heart. We also investigate the importance of glucose transporter (GLUT 1 and GLUT 4) distribution in governing the observed phosphorylated analogue accumulation. Hearts ( n=5) were perfused with Krebs buffer for 40 min, made regionally zero-flow ischaemic for 40 min and reperfused for 60 min with Krebs containing tracer (18)FDG (200 MBq) and tracer (14)C-2-DG (0.37 MBq). Hearts were then frozen and five sections (10 micro m) were cut per heart, fixed and exposed on phosphor storage plates for 18 h (for (18)FDG) and then for a further 9 days (for (14)C-2-DG). Quantitative digital images of tracer accumulation were obtained using a phosphor plate reader. The protocol was repeated in a second group of hearts and GLUT 1 and GLUT 4 distribution analysed. Post-ischaemic accumulation of (18)FDG-6-P was inhibited by 38.2%+/-1.7% and (14)C-DG-6-P by 19.0%+/-2.2%, compared with control ( P<0.05). After placing seven "lines of interrogation" across each heart section and analysing the phosphorylated tracer accumulation along them, a transmural gradient of both tracers was observed; this was highest at the endocardium and lowest at the epicardium. GLUT 4 translocated to the sarcolemma in the ischaemic/reperfused region (from 24%+/-3% to 59%+/-5%), while there was no cellular redistribution of GLUT 1. We conclude that since decreased phosphorylated tracer accumulation occurs after ischaemia-reperfusion, despite greater externalisation of GLUT 4, hexokinase or the affinities of the GLUT transporters are changed under these conditions.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:Dissociation of glucose tracer uptake and glucose transporter distribution in the regionally ischaemic isolated rat heart: application of a new autoradiographic technique. 1227 16

A dual-isotope simultaneous acquisition (DISA) single-photon emission tomography (SPET) protocol with fluorine-18 fluorodeoxyglucose ((18)F-FDG) and a technetium-99m labelled flow tracer is attractive because it permits assessment of both myocardial glucose utilisation and flow within a single study. Differences in physical and physiological characteristics between (18)F-FDG and the (99m)Tc-labelled flow tracer, however, may cause differences in myocardial activity distribution between the agents. The aim of this study was to investigate the relation between the myocardial distribution of (18)F-FDG and a (99m)Tc-labelled flow tracer on DISA SPET in comparison with nitrogen-13 ammonia/(18)F-FDG positron emission tomography (PET). Nine normal volunteers without cardiac disease and ten patients with known coronary artery disease (CAD) underwent (13)N-ammonia/(18)F-FDG PET and (99m)Tc-sestamibi/(18)F-FDG DISA SPET. Using a semiquantitative polar map approach, the left ventricular myocardium was divided into nine segments, and relative regional activity was calculated for each segment. A segment was considered to have concordant uptake between (18)F-FDG and flow tracer if the difference in measured regional activity between the tracers was < or =10% of peak activity, and the percentage of concordant segments was calculated for each subject. There was a good overall concordance of myocardial activity between the agents on DISA SPET (84.0%+/-14.8%) in normals, which was comparable to that seen on PET (86.4%+/-14.5%, NS vs DISA SPET). However, the myocardial activity distributions of (18)F-FDG and flow tracer were not identical in that reduced flow tracer activity was seen in the basal segments on DISA SPET in both normals and CAD patients. It is concluded that there is good overall concordance of activity between (18)F-FDG and flow tracer in normal myocardium on DISA SPET, which is comparable to that on PET, supporting the use of combined (99m)Tc-flow tracer/(18)F-FDG imaging for the detection of viable myocardium. However, there is a difference in the myocardial activity distribution between the agents in both normals and CAD patients, the difference being particularly evident in the basal segments. Therefore, careful image interpretation that takes into consideration the different normal activity distribution between the tracers and/or a tracer-specific normal database is necessary for comparison with patient studies.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:Myocardial distribution of (18)F-FDG and (99m)Tc-sestamibi on dual-isotope simultaneous acquisition SPET compared with PET. 1227 19

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

Conventional MRI often fails to distinguish between progressive tumour and radiation injury, because both appear as mass lesions with unspecific Gd-DTPA enhancement. Furthermore, the sensitivity of FDG PET for the evaluation of malignant lesions in the brain is limited owing to high cortical uptake. The aim of this study was to assess the potential of alternative SPET tracers in the same group of patients. 35.2+/-20.1 months after stereotactic radiotherapy (59.3+/-4.2 Gy) of low-grade astrocytomas (median WHO II), 16 patients, presenting 25 Gd-DTPA-enhancing lesions on MRI, were examined by SPET. Lesions were classified as progressive tumour (PT, n=17) or non-PT (nPT, n=8) based on prospective follow-up (clinical examination, MRI, proton-MR spectroscopy) for 25.6+/-6.7 months after SPET. SPET scans were performed 15 and 60 min after injection of 694+/-67 MBq hexakis(2-methoxyisobutylisonitrile)(99m)Tc(I) (MIBI). 3-[(123)I]iodo-alpha-methyl- L-tyrosine (IMT) SPET was acquired 15 min after injection of 291+/-58 MBq IMT. Lesion-to-normal tissue ratios (l/n) for IMT (l/n(IMT)) and MIBI (l/n(MIBI)) were calculated using a reference region mirrored to the contralateral hemisphere. Using IMT, significantly higher ratios ( P<0.001) were found in PT (1.7+/-0.4) than in nPT (1.1+/-0.1). For MIBI, there was no statistically significant difference ( P=0.206) between PT (3.7+/-2.8) and nPT (1.8+/-1.8). Sensitivities for MIBI and IMT were 53% and 94%, and specificities 75% and 100%, respectively. Positive predictive values for MIBI and IMT respectively reached 80% and 100%, and negative predictive values were 46% and 90%. In conclusion, in contrast to MIBI, IMT showed almost no overlap between the PT and the nPT group. The sensitivity, specificity and predictive values of IMT SPET were obviously higher than those of MIBI SPET. IMT is considered to be a useful tracer for differentiating PT from nPT in the follow-up of irradiated low-grade astrocytomas.
Eur J Nucl Med Mol Imaging 2002 Nov
PMID:Detection of tumour progression in the follow-up of irradiated low-grade astrocytomas: comparison of 3-[123I]iodo-alpha-methyl- L-tyrosine and 99mTc-MIBI SPET. 1239 64


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