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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

Stereotactic radiosurgery (SRS) using the Leksell gamma knife promotes acute and chronic local changes in glucose metabolism. We have been able to find very few papers on Medline on the subject of assessment of metastases by 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) after SRS. The aim of this work was to specify the additional value of FDG PET, in comparison with magnetic resonance imaging (MRI), in differentiating SRS-induced radionecrosis from viable brain metastasis in a clinical setting. Fifty-seven metastases in 25 patients were treated by SRS. An average of 33 weeks later, all the patients underwent FDG PET. At the same time (SD=2 weeks) all the patients underwent MRI. The sensitivity, specificity and accuracy of both FDG PET and MRI examinations were calculated with reference to clinical and radiological follow-up or biopsies. The additional value derived from use of FDG PET after MRI was assessed and progression-free survival rates were compared. The difference in progression-free survival rates between the negative and positive subgroups was significant ( P=0.0005) for MRI and even more so ( P<0.00001) for FDG PET. Sensitivity, specificity and accuracy were 75% (6/8), 93.9% (46/49) and 91.2% (52/57) for FDG PET, and 100% (8/8), 65.3% (32/49) and 70.2% (40/57) for MRI. In the subgroup of patients with positive or non-diagnostic MRI, the probability of presence of a viable tumour was only 32% (8/25). This probability increased to 100% (5/5) when subsequent FDG PET was positive and decreased to 11.1% (2/18) when FDG PET was negative. The frequency of a viable neoplasm was significantly different ( P=0.001) in the FDG PET negative and positive subgroups. MRI and FDG PET both have an important predictive value for persistent viable metastases after treatment by SRS. Neither sensitive but non-specific MRI nor specific but insensitive FDG PET is reliable on its own. While FDG PET significantly improved the diagnostic accuracy in the subgroup of patients with positive and non-diagnostic MRI, it provided no additional value in the MRI-negative subgroup.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumour progression? 1248 15

The fact that fluorine-18 fluorodeoxyglucose ([(18)F]FDG) accumulates in inflammatory lesions as well as in tumours reduces the diagnostic specificity of positron emission tomography (PET) in oncology. The aim of this study was to characterise the uptake of [(18)F]FDG in isolated human monocyte-macrophages (HMMs) in vitro in comparison with that in human glioblastoma (GLI) and pancreatic carcinoma cells (PAN). The purity of HMM preparations was determined by immunohistochemical staining and their functional integrity was assessed by long-term incubation with iodine-131 acetylated bovine serum albumin. [(18)F]FDG uptake in HMMs was quantified as percent of whole [(18)F]FDG activity per well (% ID) or as % ID in relation to total protein mass. [(18)F]FDG uptake in HMMs significantly increased with culture duration, yielding 7.5%+/-0.9% (% ID/100 micro g) at day 14. Stimulation by lipopolysaccharide further enhanced [(18)F]FDG uptake in HMMs by a factor of 2. [(18)F]FDG uptake significantly decreased with increasing glucose concentration in the medium. Radio-thin layer chromatography of intracellular metabolites revealed that [(18)F]FDG was trapped by HMMs mainly as [(18)F]FDG-6-phosphate and [(18)F]FDG-1,6-diphosphate. [(18)F]FDG uptake was in the range of uptake values measured in GLI and PAN. By accumulating [(18)F]FDG in a manner analogous to uptake by tumour cells, activated HMMs may contribute to the [(18)F]FDG uptake values measured by PET in neoplasms.
Eur J Nucl Med Mol Imaging 2003 Feb
PMID:Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro. 1255 45

Gastric cancer carries a poor prognosis and is the second most frequent cause of cancer-related death worldwide. In spite of the clinical importance of this tumour entity, only a few fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) studies have been published on gastric carcinomas. The aim of this study was to characterise the FDG uptake of gastric carcinomas by relating it to the histopathological properties of the tumours. Within this context, we focussed particularly on the microscopic growth type according to Lauren since our preliminary observations indicated low FDG accumulation in the non-intestinal growth type compared with the intestinal type. Forty patients with locally advanced gastric carcinomas and ten control subjects were studied by FDG PET (300 MBq i.v., emission scan: 40 min p.i., one bed position, measured transmission, filtered back-projection). Detectability of the tumours was qualitatively assessed by two independent observers. For quantitative analysis the regional tumour uptake was measured by standardised uptake values (SUV normalised to the body surface area) using a region of interest technique. Qualitative and quantitative analyses were performed with respect to the microscopic growth type according to Lauren (intestinal type vs non-intestinal type). Other histopathological characteristics were also assessed: mucus content, grading, tumour extension and tumour location. In 36 patients the survival rates were compared for detectable vs non-detectable tumours and for tumour FDG uptake above and below the median. Only 24 of the 40 locally advanced gastric carcinomas (60%) were detected by FDG PET. The detection rate for tumours of the intestinal type was significantly higher than that for tumours of the non-intestinal type (83% vs 41%, P=0.01). Only 2/18 intestinal type tumours contained extracellular or intracellular mucus whereas 17/22 non-intestinal tumours did so (P<0.01). The mean SUV was significantly different between the intestinal type and the non-intestinal type (6.7+/-3.4 vs 4.8+/-2.8, P=0.03), between non-mucus-containing tumours and mucus-containing tumours (7.2+/-3.2 vs 3.9+/-2.1, P<0.01) and between grade 2 tumours and grade 3 tumours (7.4+/-2.3 vs 5.2+/-3.3, P=0.02). The survival rate was not significantly different in patients with detectable tumours on FDG PET and patients with non-detectable tumours (P=0.85). It is concluded that advanced malignant tumours with a poor prognosis may show low FDG uptake due to special histopathological characteristics. The overall low detection rate of gastric carcinomas is attributable to the frequent occurrence of diffusely growing and mucus-containing tumour types. This may limit the value of FDG PET for diagnosis and therapy monitoring in patients with gastric carcinomas. Furthermore, the intensity of tumour FDG uptake is not predictive of survival in gastric carcinomas.
Eur J Nucl Med Mol Imaging 2003 Feb
PMID:FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. 1255 48

Radionuclide myocardial perfusion imaging (MPI) has been on the rise in Europe and the USA. Details on nuclear cardiology in the Czech Republic are not available as yet, as it is impossible to obtain comprehensive data from official registers owing to different methods of reporting and data evaluation. A questionnaire concerning nuclear cardiology activity and practice in 2001 was sent to all nuclear medicine departments in the Czech Republic. All 48 departments completed the questionnaire. In 2001, 50 planar and 54 tomographic (SPET) scintillation cameras were used. The average age of the SPET cameras was 5 years (13% of SPET cameras were >8 years old). Out of the 48 centres, 39 (81%) provided a nuclear cardiology service; the total number of cardiological studies was 15,740 in 2001 (1.5 studies/1,000 population/year). The most frequently employed method was MPI (81.7%), the frequency of which had increased by 10% compared with 2000; 26 of the 39 (67%) departments reported that MPI activity was increasing. Nevertheless, the Czech Republic nuclear cardiology activity remained below the European average (2.2/1,000 population in 1994) and, particularly, below activity in the USA (15/1,000 in 1997). The activity was rather unevenly spread. Whereas two centres with >1,000 studies/year accounted for 20% of the total MPI studies, 16 of 39 (41%) departments exhibited low activity (<200 studies/year) and accounted for only 15% of the total MPI studies. The use of SPET increased from 91% in 2000 to 94% in 2001 (only three institutes performed planar examinations). The most widely used tracer was (99m)Tc-MIBI (60% of total MPI), followed by (201)Tl (21%) and (99m)Tc-tetrofosmin (19%). ECG-gated SPET was employed by 20/39 (51%) centres, of which 11 (28%) performed it as a standard examination; 39% of the total MPI studies included this technique. Thirteen percent (5/39) of the departments used attenuation correction, and 69% (27/39) of the departments used a prone projection. Equilibrium radionuclide ventriculography, with 2,317 examinations (14.7%), ranked second among all nuclear cardiology methods, followed by first-pass angiocardiography (406 studies, 2.6%) and (18)F-FDG (163 studies, 1%).
Eur J Nucl Med Mol Imaging 2003 Feb
PMID:Activity and practice of nuclear cardiology in the Czech Republic, 2001. 1255 54

In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes.
Eur J Nucl Med Mol Imaging 2003 Feb
PMID:Is central benzodiazepine receptor imaging useful for the identification of epileptogenic foci in localization-related epilepsies? 1255 55

We investigated the relationship between the presence of extratemporal hypometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and seizure outcome after temporal lobectomy in patients with medically intractable temporal lobe epilepsy (TLE). In 47 patients with intractable unilateral mesial TLE, regional metabolic changes on FDG PET images obtained during the 2 months preceding anterior temporal lobectomy were compared with postoperative seizure outcome. Postoperative seizure outcome was evaluated with a mean follow-up period of 6.1+/-0.6 years (range 5.2-7.2 years). Forty-two (89%) of the 47 patients achieved a good postoperative seizure outcome (Engel class I or II). All patients had hypometabolism in the temporal cortex ipsilateral to the epileptogenic region on FDG PET scans. Fourteen (78%) of the 18 patients with hypometabolism only in the ipsilateral temporal cortex were completely seizure free (Engel class Ia) after surgery. In contrast, five (45%) of the 11 patients with extratemporal cortical hypometabolism confined to the ipsilateral cerebral hemisphere and only four (22%) of the 18 patients with hypometabolism in the contralateral cerebral cortex were completely seizure free after surgery. The postoperative seizure-free rates were significantly different across the three groups of patients with different cortical metabolic patterns ( P<0.005). Furthermore, all of the nine patients with a non-class I outcome (Engel class II-IV) had extratemporal (including contralateral temporal) cortical hypometabolism. Thalamic hypometabolism was noted in 20 (43%) of the 47 patients (ipsilateral in 12, bilateral in 8). Sixteen (59%) of the 27 patients with normal thalamic metabolism were completely seizure free after surgery, while only seven (35%) of the 20 patients with thalamic hypometabolism became completely seizure free ( P<0.05). Multivariate analysis revealed that among variables including clinical, EEG, magnetic resonance imaging, pathological and FDG PET metabolic findings, only cortical metabolic pattern was an independent factor for the prediction of postoperative seizure outcome ( P<0.005). It is concluded that extratemporal cortical hypometabolism outside the seizure focus, in particular hypometabolism in the contralateral cerebral cortex, may be associated with a poorer postoperative seizure outcome in TLE and may represent underlying pathology that is potentially epileptogenic. Thalamic hypometabolism, which was associated, but not independently, with a higher likelihood of postoperative seizures, may be secondary to extratemporal or temporal pathology.
Eur J Nucl Med Mol Imaging 2003 Apr
PMID:Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy. 1255 48

To reduce potential mis-registration from differences in the breathing pattern between two complementary PET and CT data sets, patients are generally allowed to breathe quietly during a dual-modality scan using a combined PET/CT tomograph. Frequently, however, local mis-registration between the CT and the PET is observed. We have evaluated the appearance, magnitude, and frequency of respiration-induced artefacts in CT images of dual-modality PET/CT studies of 62 patients. Combined PET/CT scans during normal respiration were acquired in 43 subjects using single- or dual-slice CT. Nineteen patients were scanned with a special breathing protocol (limited breath-hold technique) on a single-slice PET/CT tomograph. All subjects were injected with approximately 370 MBq of FDG, and PET/CT scanning commenced 1 h post injection. The CT images were reconstructed and, after appropriate scaling, used for on-line attenuation correction of the PET emission data. We found that respiration artefacts can occur in the majority of cases if no respiration protocol is used. When applying the limited breath-hold technique, the frequency of severe artefacts in the area of the diaphragm was reduced by half, and the spatial extent of respiration-induced artefacts was reduced by at least 40% compared with the acquisition protocols without any breathing instructions. In conclusion, special breathing protocols are effective and should be used for CT scans as part of combined imaging protocols using a dual-modality PET/CT tomograph. The results of this study can also be applied to multi-slice CT to potentially reduce further breathing artefacts in PET/CT imaging and to improve overall image quality.
Eur J Nucl Med Mol Imaging 2003 Apr
PMID:Dual-modality PET/CT imaging: the effect of respiratory motion on combined image quality in clinical oncology. 1258 13

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.
Eur J Nucl Med Mol Imaging 2003 Apr
PMID:Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients. 1258 76

Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [(18)F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [(18)F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10(6) Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [(18)F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [(18)F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [(18)F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [(18)F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [(18)F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.
Eur J Nucl Med Mol Imaging 2003 May
PMID:[(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction? 1260 98


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