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We compared the accuracy of fluorine-18 labelled 2-fluoro-2-deoxy- d-glucose positron emission tomography ((18)FDG PET) with that of technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy (LS) in the detection of infected hip prosthesis. Seventeen patients with a hip prosthesis suspected for infection were prospectively included and underwent (99m)Tc-methylene diphosphonate bone scintigraphy (BS), LS and an (18)FDG-PET scan within a 2-week period. Seven volunteers with ten asymptomatic hip prostheses were used as a control group and underwent BS and an (18)FDG-PET scan. Bacteriology of samples obtained by surgery or by needle aspiration and/or clinical follow-up for up to 6 months were used as the gold standard. Planar images of BS and LS (4 and 24 h p.i.) were acquired, followed by single-photon emission tomography (SPET) LS images (after 4 h). These images were scored as positive or negative by two experienced readers. The (18)FDG-PET scans of the patients were compared with the tracer distribution pattern in the asymptomatic control group and with BS. A phantom study was performed in order to identify artefacts. For this purpose, three different attenuation correction methods were tested. The combined analysis of the planar BS and LS resulted in a 75% sensitivity and a 78% specificity. The SPET LS images showed a better lesion contrast, resulting in an 88% sensitivity and a 100% specificity, while 24-h planar images were of no additional value. The analysis of PET images alone resulted in an 88% sensitivity and a 78% specificity. The combination of (18)FDG-PET and BS images resulted in an 88% sensitivity and a 67% specificity. Given the presence of small errors near the edge of the metal, which can induce significant artefacts in the corrected emission image, we decided to use the data without attenuation correction. In this preliminary study, (18)FDG-PET scans alone showed the same sensitivity as combined BS and LS, although the specificity was slightly lower.
Eur J Nucl Med Mol Imaging 2003 May
PMID:The value of (18)FDG-PET for the detection of infected hip prosthesis. 1261 22

Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.
Eur J Nucl Med Mol Imaging 2003 Mar
PMID:Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours. 1263 68

Over the years several analytical methods have been proposed for the measurement of glucose metabolism using fluorine-18 fluorodeoxyglucose ([(18)F]FDG) and positron emission tomography (PET). The purpose of this study was to evaluate which of these (often simplified) methods could potentially be used for clinical response monitoring studies in breast cancer. Prior to chemotherapy, dynamic [(18)F]FDG scans were performed in 20 women with locally advanced ( n=10) or metastasised ( n=10) breast cancer. Additional PET scans were acquired after 8 days ( n=8), and after one, three and six courses of chemotherapy ( n=18, 10 and 6, respectively). Non-linear regression (NLR) with the standard two tissue compartment model was used as the gold standard for measurement of [(18)F]FDG uptake and was compared with the following methods: Patlak graphical analysis, simplified kinetic method (SKM), SUV-based net influx constant ("Sadato" method), standard uptake value [normalised for weight, lean body mass (LBM) and body surface area (BSA), with and without corrections for glucose (g)], tumour to non-tumour ratio (TNT), 6P model and total lesion evaluation (TLE). Correlation coefficients between each analytical method and NLR were calculated using multilevel analysis. In addition, for the most promising methods (Patlak, SKM, SUV(LBMg) and SUV(BSAg)) it was explored whether correlation with NLR changed with different time points after the start of therapy. Three methods showed excellent correlation ( r>0.95) with NLR for the baseline scan: Patlak10-60 and Patlak10-45 ( r=0.98 and 0.97, respectively), SKM40-60 ( r=0.96) and SUV(LBMg) ( r=0.96). Good correlation was found between NLR and SUV-based net influx constant, TLE and SUV(BSAg) (0.90< r<0.95). The 6P model and TNT had the lowest correlation ( r<or=0.84). SUV was least accurate in predicting changes in [(18)F]FDG uptake over time during therapy. For all methods, correlation with NLR was significantly lower for bone metastases than for other (primary or metastatic) tumour lesions ( P<0.05). In conclusion, three methods with different degrees of complexity appear to be promising alternatives to NLR for measuring glucose metabolism in breast cancer: Patlak, SKM and SUV (normalised for LBM and with a correction for plasma glucose).
Eur J Nucl Med Mol Imaging 2003 May
PMID:Measuring [(18)F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. 1264 May 56

The aim of this prospective study was to compare fluorine-18 fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) with magnetic resonance imaging (MRI) in patients with early aortitis, at the time of initial diagnosis and during immunosuppressive therapy. The study population consisted of 15 patients (nine females and six males; median age 62 years, range 26-76 years) who presented with fever of unknown origin or an elevated erythrocyte sedimentation rate or elevated C-reactive protein and who showed pathological aortic [(18)F]FDG uptake. Fourteen of these patients had features of early giant cell arteritis (GCA), while one had features of early Takayasu arteritis. During follow-up, seven PET scans were performed in six patients with GCA 4-30 months (median 19 months) after starting immunosuppressive medication. The results of [(18)F]FDG imaging were compared with the results of MRI at initial evaluation and during follow-up and with the clinical findings. At baseline, abnormal [(18)F]FDG uptake was present in 59/104 (56%) of the vascular regions studied in 15 patients. Seven follow-up PET studies were performed in six patients. Of 30 regions with initial pathological uptake in these patients, 24 (80%) showed normalisation of uptake during follow-up. Normalisation of [(18)F]FDG uptake correlated with clinical improvement and with normalisation of the laboratory findings. All except one of the patients with positive aortic [(18)F]FDG uptake were investigated with MRI and MRA. Thirteen of these 14 patients showed inflammation in at least one vascular region. Of 76 vascular regions studied, 41 (53%) showed vasculitis on MRI. Of 76 vascular regions studied with both PET and MRI, 47 were concordantly positive or negative on both modalities, 11 were positive on MRI only and 18 were positive on PET only. MRI was performed during follow-up in six patients: of 17 regions with inflammatory changes, 15 regions remained unchanged and two showed improvement. Whole-body [(18)F]FDG PET is valuable in the primary diagnosis of early aortitis. The results of [(18)F]FDG PET and MRI in the diagnosis of aortitis in this study were comparable, but FDG imaging identified more vascular regions involved in the inflammatory process than did MRI. In a limited number of patients [(18)F]FDG PET was more reliable than MRI in monitoring disease activity during immunosuppressive therapy.
Eur J Nucl Med Mol Imaging 2003 May
PMID:Early diagnosis and follow-up of aortitis with [(18)F]FDG PET and MRI. 1267 2

The aim of this study was to evaluate the Melanoblastoma-bearing Libechov Minipigs (MeLiM) as an animal model of melanoma for in vivo imaging. Serial whole-body 2-deoxy-2-[(18)F]fluoro- d-glucose positron emission tomography (FDG PET) scans were conducted on five MeLiM. In order to explore different clinical stages of the tumoural lesions, each animal was scanned two to four times, at intervals of 30-155 days. PET images were analysed by a semiquantitative method based on the tumour to muscle metabolic ratio. Histology was performed on biopsies taken between or after the scans and the histological grading of the tumours was compared with the FDG uptake. The overall sensitivity of FDG PET for the detection of cutaneous melanoma was 75%; 62.5% of involved lymph nodes were positive. Sensitivity was better for tumours with vertical growth than for flat lesions. FDG PET did not detect tumours with epidermal involvement only, nor did it detect small metastatic foci. The metabolic ratio was correlated with the evolution of the melanoma. FDG PET is effective in the staging of cutaneous melanoma and the follow-up of tumoural extension and regression in Melanoblastoma-bearing Libechov Minipigs. The results obtained in this animal model correlate well with those described in human melanoma. Accordingly, this model may be useful in testing new tracers specific for melanoma and in helping to detect molecules expressed early during tumoural regression.
Eur J Nucl Med Mol Imaging 2003 Jun
PMID:A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspect and histological classification in Melanoblastoma-bearing Libechov Minipigs. 1268 88

Lymphomas are a heterogeneous group of diseases with differing histopathology, clinical behaviour, response to therapy and outcome. Lymphomas are highly sensitive to chemotherapy and radiotherapy, and the recent developments in treatment have considerably improved clinical outcome. However, there is increasing recognition that this has been at the cost of long-term treatment-related effects in a relatively young patient population. Thus, one of the most challenging aspects in the imaging of lymphoma patients is tailoring the intensity of the treatment to the individual patient. This paper reviews recently published data concerning the use of fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for therapy monitoring in lymphoma patients and highlights the shortcomings and future directions. A temporary strategy for the implementation of [(18)F]FDG-PET in the management of lymphoma patients is proposed.
Eur J Nucl Med Mol Imaging 2003 Jun
PMID:Positron emission tomography with [(18)F]FDG for therapy response monitoring in lymphoma patients. 1270 31

Metabolic or molecular imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has emerged as a powerful imaging modality for diagnosis, staging, and therapy monitoring of a variety of cancers. The accuracy of FDG-PET as an imaging tool for the primary staging of lymphoma suffers from the absence of a reference criterion to which all imaging modalities can be compared. For ethical reasons, pathological diagnosis is usually not possible for all of the lesions and abnormalities found. In this article, the current state of the art for staging of primary lymphoma is reviewed and the implications for staging and the impact on patient management discussed. Whole-body PET using FDG is superior to conventional staging, i.e., physical examination, laboratory tests, plain radiography, and CT, by 10-20%. The sensitivity of FDG-PET varies for different regions of the body and appears lowest for infradiaphragmatic disease involvement. Staging with metabolic imaging leads in 10-40% of patients to a change in clinical stage. Highly variable results have been reported on whether up- or downstaging of lymphoma with PET leads to changes in the therapeutic approach for primary lymphoma.
Eur J Nucl Med Mol Imaging 2003 Jun
PMID:PET for staging of Hodgkin's disease and non-Hodgkin's lymphoma. 1271 22

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast cancer). It is concluded that [(18)F]FDG PET with hybrid PET scanners is superior to CT and MRI in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement, whereas it is inferior to ultrasound in the detection of cervical lymph node metastasis.
Eur J Nucl Med Mol Imaging 2003 Jul
PMID:[18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods. 1273 70

Fluorine-18 labelled fluoro-2-deoxy- d-glucose ((18)FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [(18)F]3'-deoxy-3'-fluorothymidine ((18)FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of (18)FLT and (18)FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both (18)FDG and (18)FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours ( n=6) were visualised by both tracers, with (18)FDG showing on average twice the uptake of (18)FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with (18)FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for (18)FLT, compared with 31 (97%) for (18)FDG. No correlation was seen between the uptake of the two tracers ( R(2)=0.03). (18)FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that (18)FDG and (18)FLT image two distinct processes. The prognostic implications of the uptake of (18)FLT need to be assessed in terms of response to chemoradiotherapy and survival.
Eur J Nucl Med Mol Imaging 2003 Jul
PMID:Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer. 1273 71

3-O-Methyl-6-[(18)F]fluoro-L-DOPA (OMFD) is a major metabolite of 6-[(18)F]fluoro-L-DOPA. Although synthesis of OFMD was primarily established to study the dopaminergic system, as it is an amino acid analogue, uptake in experimental tumours has been found. The aim of this study was to evaluate the applicability of OMFD for brain tumour imaging and to obtain initial estimates of whole-body biodistribution and radiation dosimetry in humans. Nineteen patients with suspected or confirmed brain tumours were investigated with OMFD and dynamic brain PET, complemented by whole-body PET in seven patients. Tracer kinetics were compared for normal brain and intracerebral lesions. Tissue accumulation was quantified with standardised uptake values (SUVs). Whole-body distribution in combination with tracer kinetics from animal experiments was used for the calculation of radiation dosimetry data. On the basis of OMFD PET, viable brain tumour was suspected in 16 patients with SUVs of 3.0+/-0.8 and a tumour to non-tumour ratio of 1.9+/-0.5. Highest tumour and normal brain uptake occurred between 15 and 30 min, with a subsequent slow decrease. Late whole-body tracer distribution was uniform without specific organ accumulation. Elimination occurred via urine. The mean radiation dose to the whole body was estimated at 0.016 mSv/MBq, with the kidneys as dose-critical organ (0.033 mGy/MBq). In conclusion, OMFD enables the visualisation of brain tumours with SUVs similar to other fluorinated amino acids. The whole-body radiation exposure from OMFD is comparable to that from FDG imaging.
Eur J Nucl Med Mol Imaging 2003 Jul
PMID:3-O-methyl-6-[18F]fluoro-L-DOPA and its evaluation in brain tumour imaging. 1276 33


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