Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia

Fluorine-18 labelled fluoromisonidazole ([¹⁸F]FMISO) has been shown to accumulate in hypoxic tissue in inverse proportion to tissue oxygenation. In order to evaluate the potential of [¹⁸F]FMISO as a possible positron emission tomography (PET) tracer for imaging of liver tissue hypoxia, we measured the [¹⁸F]FMISO uptake in 13 domestic pigs using dynamic PET scanning. Hypoxia was induced by segmental arterial hepatic occlusion. During the experimental procedure the fractional concentration of inspired oxygen (FiO₂) was set to 0.67 in group A (n=6) and to 0.21 in group B (n=7) animals. Before and after arterial occlusion, the partial pressure of O₂ in tissue (TPO₂) and the arterial blood flow were determined in normal flow and flow-impaired liver segments. Standardised uptake values [SUV=kBq tissue (in g) / body weight (in kg) × injected dose (in kBq)] for [¹⁸F]FMISO were calculated from PET images obtained 3 hours after injection of about 10 MBq/kg body weight [¹⁸F]FMISO. Immediately before PET scanning, the mean arterial blood flow was significantly decreased in arterially occluded segments [group A: 0.41 (0.32–0.52); group B: 0.24 (0.16–0.33) ml min^–1 g^–1] compared with normal flow segments [group A: 1.05 (0.76–1.46); group B: 1.14 (0.83–1.57) ml min^–1 g^–1; geometric mean (95% confidence limits); P<0.001 for both groups]. After PET scanning, the TPO₂ of occluded segments (group A: 5.1 (4.1–6.4); group B: 3.5 (2.6–4.9) mmHg] was significantly decreased compared with normal flow segments [group A: 26.4 (21.2–33.0); group B: 18.2 (13.3–25.1) mmHg; P<0.001 for both groups]. During the 3-h PET scan, the mean [¹⁸F]FMISO SUV determined in occluded segments increased significantly to 3.84 (3.12–4.72) in group A and 5.7 (4.71–6.9) in group B, while the SUV remained unchanged in corresponding normal liver tissue [group A: 1.4 (1.14–1.71); group B: 1.31 (1.09–1.57); P<0.001 for both groups]. Regardless of ventilation conditions, a significant inverse exponential relationship was found between the TPO₂ and the [¹⁸F]FMISO SUV (r ²=0.88, P<0.001). Our results suggest that because tracer delivery to hypoxic tissues was maintained by the portal circulation, the [¹⁸F]FMISO accumulation in the liver was found to be directly related to the severity of tissue hypoxia. Thus, [¹⁸F]FMISO PET allows in vivo quantification of pig liver hypoxia using simple SUV analysis as long as tracer delivery is not critically reduced. Received 27 July and in revised form 28 September 1998     

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodontitis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental caries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively.¹⁸F-fluoride ion bone scan done in three patients showed that¹⁸F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy.     

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue.

To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.     

Fluorine-18 fluoromisonidazole tumour to muscle retention ratio for the detection of hypoxia in nasopharyngeal carcinoma

In vivo demonstration of hypoxia is of significance for tumour patient management. Fluorine-18 fluoromisonidazole ([¹⁸F]FMISO) is a proven hypoxie imaging agent. We developed an [¹⁸F]FMISO tumour to muscle retention ratio (TMRR) for the detection of tumour hypoxia in nasopharyngeal carcinoma (NPC). Data were acquired by positron emission tomography (PET) of the nasopharynx and neck after intravenous injection of 370 MBq of [¹⁸F]FMISO. Two imaging protocols were adopted: a long protocol for comprehensive dynamic information and a short protocol for a simple, clinically convenient imaging procedure. Tomograms were reconstructed and evaluated visually. ROI analysis on the basis of time-activity curve evaluation was performed to calculate the TMRR of NPC or cervical nodal metastases (CNMs) in relation to the suboccipital muscles at 2 h. The calculation of the TMRR was exactly the same for both the long and the short protocol as two 30-min composite frames had been created immediately after intravenous injection and 2 h after injection of [¹⁸F]FMISO in the long protocol. The normal tissue to muscle retention ratio (NTMRR) was derived similarly from the normal nasopharynx. The data of 12 controls and 24 patients with NPC were analysed. The long protocol was used in 15 patients, and the short protocol in nine. In controls, the mean NTMRR±1 SD was 0.96±0.14. The mean TMRRs for NPC and CNMs were 2.56±1.50 and 1.35±0.51, respectively; these values were significantly higher than the mean NTMRR for normal controls (P<0.005 in each case). At the retention threshold value of 1.24, tumour hypoxia occurred in 100% of the primary lesions of NPC and 58% of CNMs. The TMRR for undifferentiated carcinoma was significantly lower than that for non-keratinized carcinoma (P<0.05). The [¹⁸F]FMISO TMRR is a simple and clinically useful index for detecting tumour hypoxia in NPC.     

Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results

The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50–60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method. Received 5 March and in revised form 20 May 1998     

Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose

Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved.     

A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours

Thallium-201, carbon-11 methionine (MET) and fluorine-18 fluorodeoxyglucose (FDG) have all been used to assess brain tumours. The aim of this study was to determine which of these tracers are of use for evaluating the histological grade and the extent of astrocytoma. ²⁰¹Tl single-photon emission tomography (SPET), MET positron emission tomography (PET) and FDG PET were all performed in 23 patients (13 men, 10 women) with newly diagnosed astrocytic tumours [seven with astrocytoma (grade II), ten with anaplastic astrocytoma (grade III) and six with glioblastoma (grade IV)]. The ²⁰¹Tl uptake of the tumours was evaluated by a lesion-to-normal region count ratio. Both MET and FDG uptake of the tumours was evaluated by a semiquantitative analysis using the standardized uptake value. ²⁰¹Tl uptake was found to increase in rank order with histological grade and was significantly different among the three groups (grade II: 1.51±0.36; grade III: 2.58±1.50; grade IV: 7.65±3.84). MET uptake in grade II (1.49±0.44) was also significantly lower than that in both grade III (3.29±1.44) and grade IV (3.20±0.92). FDG uptake was not significantly different among the three groups (grade II: 2.90±0.45; grade III: 3.86±1.56; grade IV: 3.57±0.83). No significant correlation was observed between ²⁰¹Tl uptake and either MET uptake or FDG uptake. In most patients, the extent of the increased MET uptake was the largest while that of the increased FDG uptake was the smallest. In patients with positive ²⁰¹Tl uptake, the extent of the ²⁰¹Tl uptake was equal to or smaller than that of gadolinium enhancement. For evaluation of histological grade of astrocytic tumours. ²⁰¹Tl is therefore considered to be useful though the ²⁰¹Tl uptake in some grade III astrocytomas was not different from that in grade II astrocytomas. MET was found to be highly useful for detecting astrocytomas, for differentiating between benign and malignant astrocytomas, and for evaluating the extent of astrocytomas; however, it was not sufficiently useful permit evaluation of the histological grade. FDG was not found to be useful either for evaluating the histological grade or for differentiating between benign and malignant astrocytomas. Received 10 March and in revised form 11 May 1998     

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron mission tomography in patients with bladder cancer

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000–3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine. Present address: Department of Radiology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359, Japan     

Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization orocedures

While the evident advantages of absolute metabolic rate determinations cannot be equalled by static image analysis of fluorine-18 fluorodeoxyglucose positron emission tomographic (FDG PET) studies, various algorithms for the normalization of static FDG uptake values have been proposed. This study was performed to compare different normalization procedures in terms of dependency on individual patient characteristics. Standardized FDG uptake values (SUVs) were calculated for liver and lung tissue in 126 patients studied with wholebody FDG PET. Uptake values were normalized for total body weight, lean body mass and body surface area. Ranges, means, medians, standard deviations and variation coefficients of these SUV parameters were calculated and their interdependency with total body weight, lean body mass, body surface area, patient height and blood sugar levels was calculated by means of regression analysis. Standardized FDG uptake values normalized for body surface area were clearly superior to SUV parameters normalized. for total body weight or lean body mass. Variation and correlation coefficients of body surface area-normalized uptake values were minimal when compared with SUV parameters derived from the other normalization procedures. Normalization for total body weight resulted in uptake values still dependent on body weight and blood sugar levels, while normalization for lean body mass did not eliminate the positive correlation with lean body mass and patient height. It is concluded that normalization of FDG uptake values for body surface area is less dependent on the individual patient characteristics than are FDG uptake values normalized for other parameters, and therefore appears to be preferable for FDG PET studies in oncology.     

Radiation dose to technicians per nuclear medicine procedure: comparison between technetium-99m, gallium-67, and iodine-131 radiotracers and fluorine-18 fluorodeoxyglucose

The aim of this study was to determine the non-extremity gamma dose received by a technician while performing an ordinary nuclear medicine procedure or a static (i.e. without blood sampling) fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) study. The dose per patient was measured by means of a commercial electronic pocket Geiger Mueller dosimeter, worn in the upper left pocket of the overalls. This was previously tested by exposure to known point sources of technetium-99m, gallium-67, iodine-131 and fluorine-18 in the air. A further test was performed with ^99mTc, ¹³¹I and ¹⁸F sources inserted in a water phantom to simulate the condition of high scattering degradation of the primary radiation due to the patient’s tissues. Subsequently, the dose was measured by two technicians for a total of 314 clinical cases, covering the most common nuclear medicine procedures, including 44 static, two-level FDG PET studies with repositioning of the patient on the couch between the transmission and the emission scan and seven whole-body PET studies. The dose read by the dosimeter was corrected for environmental background and for detector efficiency measured with sources in the air. For a limited subset of cases, the time spent close to patients was also measured. Doses were then estimated by a crude non-absorbing point source approximation and by using experimental dose rates. A comparison between experimental and estimated doses, as well as with previously published data, completed the work. For most of the conventional procedures, the measured dose per procedure proved to be within the range 0.2–0.4 μSv, except for equilibrium angiocardioscintigraphy (1.0±0.5 μSv) and ^99mTc-sestamibi single-photon emission tomography (1.7±1.0 μSv). Comparison with data published in the last 20 years shows that our values are generally lower. The current more favourable working conditions are a result of technological improvements (for instance two-head gamma cameras capable of whole-body studies), and safer shielding and distance from patients. Two-level PET gave 11.5±4.4 μSv and whole-body PET 5.9±1.2 μSv. In a subset of patients these values could be subdivided into the separate contributions from each phase of the procedure. They were: 0.11±0.04 μSv for daily quality assurance, 2.9±3.0 μSv for two transmission scans, 0.3±0.1 μSv for syringe preparation, 2.8±1.8 μSv for injection and escorting the patient to the waiting room, 1.7±1.5 μSv for a whole-body emission scan, 7.7±5.2 μSv for two emission scans, and 0.8±0.2 μSv for patient departure. The higher value from PET by comparison with conventional procedures is attributable to the higher specific gamma constant of ¹⁸F, as well as the longer time required for accurate positioning. Received 11 March and in revised form 5 July 1997     

Non-invasive assessment of skeletal kinetics using fluorine-18 fluoride positron emission tomography: evaluation of image and population-derived arterial input functions

To measure regional skeletal kinetics using fluorine-18 fluoride positron emission tomography (PET) it is necessary to know the concentration of radioactive tracer being delivered to bone by arterial plasma with relation to time, the arterial input function (IFa). Methods by which IFa can be derived without arterial sampling are attractive because of their relative technical simplicity and the reduction in possible morbidity to the subject. We have compared the use of a scaled population input function (IFp) and a corrected image-derived input function from the aorta (IFi) with an IFa directly measured from a radial artery line in ten normal postmenopausal women. Both of the aforementioned methods rely only on a small number of discrete venous samples. Each subject had a dynamic PET acquisition of the lumbar spine performed after the intravenous injection of 180 MBq ¹⁸F-fluoride. Both the IFp and the IFi were compared with the IFa in terms of the accuracy of determination of six parameters. These were: plasma clearance of fluoride to bone mineral (K _i), unidirectional plasma clearance to total bone tissue (K ₁) and individual rate constants k ₂, k ₃ and k ₄, calculated using non-linear regression with a three-compartment model, and the plasma clearance to bone mineral calculated using the Patlak method (K _pat). For both the IFp and the IFi method the root mean square errors for K _pat and K _i were similar and small (<8.2%). The errors in determining K ₁ and the rate constants k ₂ to k ₄ are larger by either method, but with a small advantage using the IFp method. It is concluded that the use of either non-invasive method for determining the arterial plasma input function is suitable for the measurement of the most important parameters, K _i and K _pat, in these subjects. Received 8 April and in revised form 11 July 1999     

Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven useful in the differentiation of various tumour entities, including breast cancer. In patients with primary breast cancer we performed a 3-h imaging protocol to examine possible improvements in tumour detectability and image contrast. Twenty-nine patients with primary breast cancer with a diameter of ≥2 cm that was demonstrated to be malignant by biopsy or surgery were injected with 370–740 MBq ¹⁸F-FDG and scanned in the prone position. Data were acquired 0–40 min, 1.5 h and 3.0 h after injection. After correction for measured attenuation, decay and scatter and iterative reconstruction, standardised uptake values (SUVs) and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual analysis was performed using transverse, sagittal and coronal slices as well as 3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were significantly higher for the 3-h images than for the 1.5-h images. SUVs did not increase to the same extent. Lesion detectability was 83% in 1.5-h images compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i. Received 17 October and in revised form 8 December 1998     

Cardiac fluorine-18 fluorodeoxyglucose imaging using a dual-head gamma camera with coincidence detection: a clinical pilot study

Dual-headed gamma cameras with coincidence detection (MCD) are increasingly used for imaging of positron-emitting tracers, such as fluorine-18 fluorodeoxyglucose (FDG). In this study, we examined differences between FDG MCD and FDG positron emission tomography (PET) as the gold standard to determine whether FDG MCD could be used for assessment of myocardial viability in daily practice. Nineteen patients with a previous myocardial infarction (17 men; mean left ventricular ejection fraction 44%±13%) underwent FDG MCD, FDG PET, resting echocardiography and technetium-99m tetrofosmin gated single-photon emission tomography (SPET). At the 50% threshold value for FDG PET, the area under the receiver operating characteristic curve for FDG MCD was 0.77±0.03. In 107 dyssynergic segments on echocardiography and 151 segments with hypoperfusion on ^99mTc-tetrofosmin SPET, the specificity of FDG MCD for the detection of myocardial viability was 72% and 76% respectively, with a sensitivity of 69% and 72% respectively. Regional analysis showed a significantly lower agreement of FDG MCD and FDG PET in the inferior and septal regions (58% for dyssynergic segments and 65% for segments with hypoperfusion), as compared with the other regions (85% for dyssynergic regions, P<0.05, and 86% for segments with hypoperfusion, P<0.05). Five patients (26%), who all had a body mass index ≥25% kg/m², showed more than 25% disagreement between FDG MCD and FDG PET. Because of the moderate overall agreement with FDG PET, the low sensitivity in akinetic or dyskinetic regions and the low agreement in the inferior and septal regions, further studies and implementations of technical developments are needed before FDG MCD can be introduced into clinical practice for the assessment of myocardial viability. Received 4 December 1999 and in revised form 5 February 2000     

Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and technetium-99m methoxyisobutylisonitrile scintimammography in the detection of breast tumours

The aim of this study was to compare, in breast cancer patients, the diagnostic accuracy of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) and scintimammography (SMM) using technetium-99m methoxyisobutylisonitrile (MIBI). A total of 20 patients (40 breasts with 22 lesions) were evaluated serially with MIBI and, on the following day, with FDG. For SMM, planar and single-photon emission tomography imaging in the prone position was performed starting at 10 min following the injection of MIBI (740 MBq). For PET, scans were acquired 45–60 min after the injection of FDG (370 MBq) and attentuation correction was performed following transmission scans. Results from SMM and PET were subsequently compared with the histopathology results. True-positive results were obtained in 12/13 primary breast cancers (mean diameter=29 mm, range 8–53 mm) with both FDG and MIBI. False-negative results were obtained in two local recurrences (diameter <9 mm) with both FDG and MIBI. In benign disease, FDG and MIBI did not localize three fibrocystic lesions, two fibroadenomas and one inflammatory lesion (true-negative), but both localized one fibroadenoma (false-positive). Collectively, the results demonstrate a sensitivity of 92%, and a specificity of 86%, for primary breast cancer regardless of whether FDG or MIBI was used. In contrast to MIBI scintigraphy, FDG PET scored the axillae correctly as either positive (metastatic disease) or negative (no axillary disease) in all 12 patients. The tumour/non-tumour ratio for MIBI was 1.97 (range 1.43–3.1). The mean standard uptake value (SUV) for FDG uptake was 2.57 (range 0.3–6.2). The diagnostic accuracy of SMM was equivalent to that of FDG PET for the detection of primary breast cancer. For the detection of in situ lymph node metastases of the axilla, FDG seems to be more sensitive than^99mTc-MIBI.     

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma: A preliminary report

Thymomas are lacking in malignant cytological features. Their staging is defined by the invasiveness of the tumour. This study aimed to analyse the uptake patterns of fluorine-18 fluorodeoxyglucose (FDG) in thymomas of different stages. FDG positron emission tomography (PET) scan was performed in 12 patients suspected of having thymoma and in nine controls. Qualitative visual interpretation was used to detect the foci with FDG uptake higher than that of normal mediastinum. Tumour/lung ratio (TLR) was calculated from the counts of ROIs over the mass and over comparable normal lung tissue in thymoma patients. Mediastinum/lung ratio (MLR) was calculated from the counts of ROIs over the anterior mediastinum and lung in controls. The PET scan patterns of distribution of foci with FDG uptake and TLRs were correlated with the computed tomography (CT) or magnetic resonance imaging (MRI) findings, and staging of the thymomas. Thymectomy was performed in ten patients and thoracoscopy was done in two patients. The results revealed ten thymomas (two stage I tumours, two stage II, four stage III and two stage IV, according to the Masaoka classification), and two cases of thymic hyperplasia associated with myasthenia gravis. Myasthenia gravis was also noted in four thymoma patients. FDG studies showed (a) diffuse uptake in the widened anterior mediastinum in patients with thymic hyperplasia, (b) confined focal FDG uptake in the non-invasive or less invasive, stage I and II thymomas, and (c) multiple discrete foci of FDG uptake in the mediastinum and thoracic structures in stage III and IV advanced invasive thymomas. The thymomas had the highest TLRs, followed by the TLRs of thymic hyperplasia and the MLRs of control subjects (P <0.005). No significant difference was found between thymomas in different stages or between thymomas with and thymomas without myasthenia gravis. In comparison with CT and/or MRI, FDG-PET detected more lesions in patients with invasive thymomas and downgraded the staging of thymoma in four patients. Our preliminary results suggest that FDG-PET is useful in the assessment of the invasiveness of thymomas, and may have the potential to differentiate thymomas from thymic hyperplasia.     

Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients

Fluorine-18 deoxyglucose (FDG) is not a very tumour-specific substance, and its accumulation in benign lesions with increased glucose metabolism may give rise to false-positive results and hence cause FDG positron emission tomography (PET) to display relatively low specificity (frequently below 85%). Correct interpretation of FDG PET studies is predicated upon detailed knowledge of morphological abnormalities, and the importance of the correlation of functional and morphological information, as derived from computed tomography or magnetic resonance imaging, is discussed. It is emphasized that image fusion programs cannot substitute for understanding of functional and morphological methods. The reconstruction of PET cross-sections is considered, and it is concluded that an iterative image reconstruction method is to be favoured, given its advantages in reducing image artefacts and improving quantification of radioactivity concentrations. The differentiation of malignant and benign lesions when using FDG PET is then reviewed; false-positive findings may be obtained, for example, in patients with acute inflammatory lesions, chronic pancretitis, retroperitoneal fibrosis or salivary gland tumours. It is suggested that these problems may be alleviated by means of multitracer studies, e.g. using carbon-11 labelled aminoisobutyric acid for quantification of A-type amino acid transport. Finally, the effects of radiotherapy and chemotherapy on FDG uptake and the problems that accrue from these effects are reviewed. Both radiotherapy and chemotherapy can cause increased FDG uptake, complicating diagnosis and evaluation. Knowledge of the effects of different treatment procedures on regional FDG metabolism is therefore necessary for correct interpretation of the PET data.     

Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies imaging FDG PET imaging is used to detect and stage head and neck cancers. However, the variable physiologic uptake of FDG in different normal structures as well as at inflammatory sites may either obscure a tumor focus or be falsely interpreted to represent tumor activity. Twenty-one patients (9 men, 12 women, median age 59) were scanned serially at two time points, one at 70 min (range 47–112) and the second at 98 min (77–142) after the intravenous injection of 4.3 MBq/kg of FDG. The mean interval between emission scans was 28 min (13–49). Transmission scans were performed and regions of interest (ROIs) were overlayed on the fully corrected images. Standardiued uptake values (SUVs) were generated for the cerebellum, tongue, larynx, every lesion, and a matched contralateral site. Follow-up and pathologic studies revealed 18 squamous cell carcinomas and nine inflammatory or infectious lesions. Tumor SUVs were 4.0±1.6 (mean ± SD) for the first scan and 4.5±2.2 for the second scan. Contralateral SUVs were 1.2±0.5 and 1.1±0.5 for the two scans. Tumor SUVs increased by 12%±12% as compared with a 5%±17% decrease for contralateral sites (P<0.05). SUVs for inflammatory sites (2.0±0.7 and 2.0±0.9), cerebellum (4.2±1.3 and 4.3±1.4), tongue (1.8±0.4 and 1.9±0.5) and larynx (1.5±0.6 and 1.5±0.6) remained constant over time (+0.6%, +2.8%, +1.4%, and –2.4%; P<0.05 when compared with tumor SUV changes). The ratio tumor/contralateral SUV increased by 23%±29% over time while this ratio for inflamed sites increased by only 5%±15% (P=0.07). The time interval between scans correlated with increase in SUV for tumors (r=0.55, P<0.05) but not for any of the other ROIs. Separation was superior when studies were performed more than 30 min apart (P<0.05). These preliminary data suggest that dual time point imaging compatible with a clinical study protocol is helpful in differentiating malignant lesions from inflammation and normal tissues, especially when separated by a sufficient time interval. Received 22 March and in revised form 29 April 1999     

Staging of non-small-cell lung cancer by whole-body fluorine-18 deoxyglucose positron emission tomography

Positron emission tomography (PET) using fluorine-18 deoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has been proven useful to differentiate malignant from benign tissue. We undertook a prospective study in 61 patients to compare the accuracy of whole-body FDG PET and conventional imaging (CI) methods for the staging of nonsmall-cell lung cancer (NSCLC). CI included chest and abdomen computed tomographic scanning and bone scintigraphy. When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or clinical or radiological follow-up. As compared to CI, PET correctly changed the N stage in 13 patients (21%) and the M stage in six patients (10%). There were three false-positive and no false-negative distant PET findings. Our preliminary results show that whole-body FDG PET can improve the diagnostic accuracy in the staging of NSCLC.     

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca’s area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern. Received 16 March and in revised form 9 July 1998     

^18F-FDG PET-CT在淋巴瘤分期及疗效评价中的应用研究

目的探讨^18氟-氟代脱氧葡萄糖（^18F-FDG）PET—CT在淋巴瘤分期及疗效评价中的临床应用价值。方法回顾分析28例淋巴瘤患者（HL6例，NHL22例）在治疗前后进行^18F—FDG PET—CT对比检查的结果，并与增强CT及骨髓活检结果进行比较。结果治疗前68处病灶^18F—FDG PET—CT检出67个，检出率为98．5％，其中结内37个全部检出（100％），结外31个检出30个（96．8％）；增强CT则共检出病灶45个（66．2％），其中结内37个检出32个（86．5％），结外31个仅检出13个（41．9％）。6例（21．4％）的分期得到上调并改变了1例（3．6％）的治疗方案。治疗后32处病灶^18F—FDG PET—CT检出29个，检出率为90．6％，其中结内17个检出15个（88．2％），结外15个检出14个（93．3％）；增强CT则共检出病灶18个（56．3％），其中结内17个检出13个（76．5％）．结外15个仅检出5个（33．3％）。治疗后有2例（7．1％）的分期得到上调，8例（28．6％）下调，改变了8例（21．4％）的治疗方案。^18F—FDG PET—CT对淋巴瘤患者治疗前后结内病灶检出率与增强CT相似（P〈0．05），而结外病灶检出率则明显高于增强CT（P〉0．05）。28例中25例^18F—FDG PET—CT与骨髓穿刺结果一致。治疗后^18F—FDG PET—CT对复发的阳性预测值93．8％，阴性预测值为83．3％；增强CT的阳性预测值75％，阴性预测值50％。结论^18F—FDG PET—CT在淋巴瘤分期及疗效评价中具有重要的临床价值．有助于准确分期和残余病变性质的鉴别。