Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase

This animal study investigates the application of positron emission tomography (PET) with tracers of tumour metabolism for monitoring suicide gene therapy with herpes simplex virus thymidine kinase (HSVtk). After transplantation of HSVtk-expressing Morris hepatoma cells into ACI rats, dynamic PET measurements of 18F-labeled 2-fluoro-2-deoxyglucose (FDG) uptake were performed in animals 2 days (n = 7) and 4 days (n = 5) after the onset of therapy with 100 mg ganciclovir (GCV)/kg body weight as well as after administration of sodium chloride (n = 8). The arterial FDG plasma concentration was measured dynamically in an extracorporeal loop and the rate constants for FDG transport (K1, k2) and FDG phosphorylation (k3) were calculated using a three-compartment model modified for heterogeneous tissues. Also, quantification using the metabolic rate of FDG turnover and the standardized uptake value (SUV) was done. Furthermore, the thymidine incorporation into the tumour DNA was determined after i.v. administration of 3H-thymidine. An uncoupling of FDG transport and phosphorylation was found with enhanced K1 and k2 values and a normal k3 after 2 days of GCV treatment. The increase in FDG transport normalized after 4 days whereas the phosphorylation rate k3 increased. Quantification using the metabolic rate or the SUV showed congruent but less sensitive results compared with the modeling approach. The thymidine incorporation into the DNA of the tumours declined to 10.5% of the controls after 4 days of GCV treatment. The data indicate that PET with 18FDG and 11C-thymidine may be applied for monitoring of gene therapy with the HSVtk/GCV suicide system. Increased transport rates are evidence of stress reactions early after therapy. The measurement of thymidine incorporation into the tumour DNA can be used as an indicator of therapy efficacy.     

PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine

This study was performed to investigate the effect of the new chemotherapeutic agent gemcitabine on glucose transport and metabolism in prostate carcinoma in vitro and in vivo. METHODS: After transplantation of rat prostate adenocarcinoma cells, dynamic PET measurements with fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose (18FDG) were performed in 15 animals before and 1 day after therapy with 90 mg/kg of body weight (n = 8) and 180 mg/kg of body weight (n = 7) gemcitabine. In the second examination, the animals received a simultaneous injection of 18FDG and [3H]thymidine. Quantitative evaluation of the PET data was done using the standardized uptake value (SUV) as well as a three-compartment pharmacokinetic model. Furthermore, the incorporation of [3H]thymidine into the DNA was determined. In vitro measurements of the FDG, 3-O-methylglucose and thymidine uptake were performed immediately and 4 hr after a 24-hr incubation period with different doses of gemcitabine. RESULTS: FDG-SUV and the metabolic rate of FD 3 utilization did not change significantly after therapy. However, the values for the transport rate constants K1 and K2 increased significantly. The incorporation of thymidine into the DNA of treated tumors showed an 80% decline as compared with a control group. In the cell culture experiments, a dose-dependent increase of FDG (up to 178%) and 3-O-methylglucose uptake (up to 305%) was demonstrated. The thymidine uptake showed a 96% decline in the nucleic acid fraction and an increase of up to 337% in the cytoplasmic fraction. CONCLUSION: The more global measures of FDG metabolism as SUV and metabolic rate of FDG utilization were unchanged after therapy, while DNA synthesis and cell viability declined. However, in vitro and in vivo evidence of an enhancement of glucose transport is presented, indicating that quantification by modelling may be superior for the evaluation of metabolic effects during chemotherapy.     

Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma

The goals of our study were to establish PET accuracy with 18F-fluorodeoxyglucose (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC) and to investigate the correlation between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. MATERIALS: Twenty-nine patients with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well differentiated, 2 well-moderately differentiated, 11 moderately differentiated and 1 poorly differentiated) were studied. All patients underwent thoracotomies within 4 wk after the FDG PET study. For qualitative analysis, the degree of FDG activity in the tumors was visually scored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinal blood-pool activity, 2 = same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal blood-pool activity and 4 = substantially greater than mediastinal blood-pool activity. Foci of activity with Grades 2-4 were considered tumors. For semiquantitative analysis, standardized uptake values (SUV) were calculated. RESULTS: In 7 BACs, 4 lesions (57%) showed negative results on FDG PET, while in 23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma showed a negative result. BACs' mean visual score (1.43 +/- 1.27) was significantly lower than that of non-BACs (3.17 +/- 1.03) (p = 0.001). The BACs' mean SUV (1.36 +/- 0.821) was significantly lower than that of well-differentiated adenocarcinomas (2.92 +/- 1.28) (p = 0.014); the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (4.63 +/- 1.86) (p = 0.031). No significant differences were apparent in average size among these three histologic types. CONCLUSION: A correlation was observed between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. FDG PET may show negative results for BAC.     

Metabolism of L-phenylalanine and L-tyrosine by the phototrophic bacterium Rhodobacter capsulatus

We have investigated whether increased tumor uptake of fluorine-18 fluorodeoxyglucose (FDG) detected with positron emission tomography (PET) early after initiating tamoxifen therapy ("metabolic flare") predicts a hormonally responsive breast cancer. Eleven postmenopausal women with biopsy-proved estrogen receptor-positive (ER+) metastatic breast cancer were studied by PET with FDG and 16alpha[18F]fluoro-17beta-estradiol (FES) before and 7-10 days after initiation of tamoxifen therapy. FDG and FES uptake was evaluated semiquantitatively in 21 lesions. The PET results were correlated with follow-up evaluation, continued until the patient became unresponsive to hormone therapy (3-24 months). There were seven responders and four nonresponders based on clinical follow-up. None of the responders had a clinical flare reaction, but all demonstrated metabolic flare, with a mean +/- standard deviation increase in tumor standardized uptake value (SUV) for FDG of 1.4+/-0. 7. No evidence for flare was noted in the nonresponders (change in SUV for FDG -0.1+/-0.4; P = 0.008 vs. responders). The degree of ER blockade by tamoxifen was greater in responders (mean decrease in SUV 2.7+/-1.7) than in nonresponders (mean decrease 0.8+/-0.5) (P = 0.04). The lesions of responders had higher baseline SUVs for FES than did those of three of four nonresponders (>/=2.2 vs 相似文献   

Neck dissection in the treatment of cancer of major salivary glands

We investigated the use of PET and 2[18F]fluoro-2-deoxy-D-glucose (FDG) for detection and therapy control of metastatic germ cell cancer in comparison to CT. METHODS: Fifty-four PET studies were performed in addition to CT in 33 patients with histopathologically proven germ cell tumors (14 seminomas, 18 nonseminomas, 1 not classified). The scans were done either after initial diagnosis (Group 1; n = 12), within 2 wk after completion of chemotherapy (Group 2; n = 13) or 14-375 days after chemotherapy (Group 3; n = 29). PET and CT were validated either by histology (n = 19) or clinical follow-up for 182-1704 days (n = 35). Focal pathological uptake with PET was quantified using standardized uptake values (SUVs). RESULTS: PET was significantly more accurate than CT (0.86 versus 0.59; p < 0.025) for detection of residual viable tumor in Group 3. While sensitivities of PET and CT did not differ markedly, PET was significantly more specific than CT. No significant differences between PET and CT were found in Groups 1 and 2. PET scans after therapy resulted in false-negative findings in five of nine cases of Group 2 but only in two of nine cases of Group 3. False-positive PET findings occurred in three inflammatory processes. SUV of seminomas was significantly higher than in nonseminomas (p < 0.01). CONCLUSION: PET using FDG is superior to CT for assessment of residual tumor after chemotherapy of germ cell cancer and may thus have an increased effect on patient management in the future. PET must be performed at least 2 wk after completion of therapy. Further data are necessary to determine the role of FDG PET for initial staging of germ cell cancer.     

Bilateral medialization laryngoplasty

To investigate the possible role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in the prognostic evaluation of primary breast cancer, we studied 86 patients with T1-3 (TNM classification) breast tumours before surgery and compared the tumour FDG uptake, calculated as a standardized uptake value (SUV), with postoperative histopathological findings, steroid hormone receptor status of the tumour, thymidine labelling index (LI) and tissular expression of p53. SUV was significantly higher in infiltrating ductal carcinomas (n = 68; median SUV = 5.6) than in lobular ones (n = 18; median SUV = 3.8), and in grade 3 carcinomas (n = 26; median SUV = 6.2) than in grade 1-2 ones (n = 60; median SUV = 4.9). Moreover, SUV was significantly higher in carcinomas with high levels of p53 (n = 12; median SUV = 9.5) than in those with low levels (n = 48; median SUV = 4.25). By contrast, there was no significant correlation between SUV and the steroid hormone receptor status or LI of tumours. Our data demonstrate that FDG uptake, expressed as SUV, is associated with certain prognostic factors in breast cancer, such as histopathological grading and p53 expression, which can be assessed only by means of postoperative in vitro examinations. Hence, the information provided by FDG-PET is to some extent related to relevant information on tumour biology. The clinical value of these data will have to be confirmed by analysis of the independence of SUV from other prognostic factors by means of a multivariate analysis performed on a larger series of patients with adequate follow-up. If SUV is confirmed as an independent variable, FDG-PET could assume an important role in the determination of appropriate therapeutic strategies for primary breast cancer.     

Evaluation of benign vs malignant hepatic lesions with positron emission tomography

BACKGROUND: In most malignant cells, the relatively low level of glucose-6-phosphatase leads to accumulation and trapping of [18F]fluorodeoxyglucose (FDG) intracellularly, allowing the visualization of increased uptake compared with normal cells. OBJECTIVES: To assess the value of FDG positron emission tomography (PET) to differentiate benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. DESIGN: Prospective blinded-comparison clinical cohort study. SETTING: Tertiary care university hospital and clinic. PATIENTS: One hundred ten consecutive referred patients with hepatic lesions 1 cm or larger on screening computed tomographic (CT) images who were seen for evaluation and potential resection underwent PET imaging. There were 60 men and 50 women with a mean (+/-SD) age of 59 +/- 14 years. Follow-up was 100%. INTERVENTIONS: A PET scan using static imaging was performed on all patients. The PET scan imaging and biopsy, surgery, or both were performed, providing pathological samples within 2 months of PET imaging. All PET images were correlated with CT scan to localize the lesion. However, PET investigators were unaware of any previous interpretation of the CT scan. MAIN OUTCOME MEASURES: Visual interpretation, lesion-to-normal liver background (L/B) ratio of radioactivity, and standard uptake value (SUV) were correlated with pathological diagnosis. RESULTS: All (100%) liver metastases from adenocarcinoma and sarcoma primaries in 66 patients and all cholangiocarcinomas in 8 patients had increased uptake values, L/B ratios greater than 2, and an SUV greater than 3.5. Hepatocellular carcinoma had increased FDG uptake in 16 of 23 patients and poor uptake in 7 patients. All benign hepatic lesions (n = 23), including adenoma and fibronodular hyperplasia, had poor uptake, an L/B ratio of less than 2, and an SUV less than 3.5, except for 1 of 3 abscesses that had definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful to differentiate malignant from benign lesions in the liver. Limitations include false-positive results in a minority of abscesses and false-negative results in a minority of hepatocellular carcinoma. The PET technique was useful in tumor staging and detection of recurrence, as well as monitoring response to therapy for all adenocarcinomas and sarcomas and most hepatocellular carcinomas. Therefore, pretherapy PET imaging is recommended to help assess new hepatic lesions.     

Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography

BACKGROUND: The diagnosis of malignant mesothelioma is a challenging medical problem. CT often cannot differentiate between benign diffuse pleural thickening and malignant mesothelioma, while thoracentesis and CT-guided biopsies are insensitive. We have assessed the value of positron emission tomography (PET) with 2-fluoro-2-deoxy-D-glucose (FDG) in the evaluation of malignant mesothelioma. METHODS: Twenty-eight consecutive patients referred for the evaluation of suspected malignant mesothelioma were evaluated by FDG-PET imaging. Measured attenuation correction was performed in 26 of 28 cases for quantitation with the standardized uptake value (SUV) method. The results of PET imaging were compared with those of video-assisted thoracoscopy or surgical biopsies. RESULTS: Surgical biopsy specimens confirmed the presence of malignant disease in 24 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions (SUV=4.9+/-2.9 and SUV=1.4+/-0.6, respectively; p<0.0001). With a SUV cutoff of 2.0 to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold. FDG-PET images provided excellent delineation of the active tumor sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, 9 of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one. CONCLUSION: In this highly selected population, FDG-PET imaging was a sensitive method to identify malignant mesothelioma and determine the extent of the disease process.     

Dynamic positron emission tomography with F-18 fluorodeoxyglucose imaging in differentiation of benign from malignant lung/mediastinal lesions

PURPOSE: This study was done to evaluate the diagnostic utility of dynamic positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) imaging in patients with suspected malignant pulmonary lesions. We wanted to test the hypothesis that the rate of FDG uptake (FDG influx constant values) would differentiate malignant from benign lung or mediastinal lesions. MATERIALS AND METHODS: We performed segmental dynamic PET imaging studies following administration of FDG in 19 patients with indeterminate pulmonary lesions based on chest radiograph and/or CT scans. Patlak analysis was done to compute Ki (FDG influx constant) values and compared with FDG standardized uptake values (SUVs) and histology. RESULTS: FDG Ki values (mean+/-SD) were significantly greater (p < 0.01) in all 12 malignant lesions (0.029+/-0.02) as compared with 7 benign lesions (0.0024+/-0.0011) with good correlation to the SUV values. Distinct time activity curve patterns were identified in malignant and benign lesions with continued uptake in malignant lesions. CONCLUSION: Dynamic PET-FDG imaging accurately differentiates malignant from benign pulmonary lesions. In certain cases with equivocal findings on visual analysis and SUV values, dynamic imaging may be further helpful in differentiating benign and malignant lesions.     

2-[C-11]thymidine imaging of malignant brain tumors

Malignant brain tumors pose diagnostic and therapeutic problems. Despite the advent of new brain imaging modalities, including magnetic resonance imaging (MRI) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), determination of tumor viability and response to treatment is often difficult. Blood-brain barrier disruption can be caused by tumor or nonspecific reactions to treatment, making MRI interpretation ambiguous. The high metabolic background of the normal brain and its regional variability makes it difficult to identify small or less active tumors by FDG imaging of cellular energetics. We have investigated 2-[C-11]thymidine (dThd) and PET to image the rate of brain tumor cellular proliferation. A series of 13 patients underwent closely spaced dThd PET, FDG PET, and MRI procedures, and the image results were compared by standardized visual analysis. The resulting dThd scans were qualitatively different from the other two scans in approximately 50% of the cases, which suggests that dThd provided information distinct from FDG PET and MRI. In two cases, recurrent tumor was more apparent on the dThd study than on FDG; in two other patients, tumor dThd uptake was less than FDG uptake, and these patients had slower tumor progression than the three patients with both high dThd and FDG uptake. To better characterize tumor proliferation, kinetic modeling was applied to dynamic dThd PET uptake data and metabolite-analyzed blood data in a subset of patients. Kinetic analysis was able to remove the confounding influence of [C-11]CO2, the principal labeled metabolite of 2-[C-11]dThd, and to estimate the flux of dThd incorporation into DNA. Sequential, same-day [C-11]CO2 and [C-11]dThd imaging demonstrated the ability of kinetic analysis to model both dThd and CO2 simultaneously. Images of dThd flux obtained using the model along with the mixture analysis method for pixel-by-pixel parametric imaging significantly enhanced the contrast of tumor compared with normal brain. Comparison of model estimates of dThd transport versus dThd flux was able to discern increased dThd uptake simply on the basis of blood-brain barrier disruption retention on the basis of increased cellular proliferation. This preliminary study demonstrates the potential for imaging brain tumor cellular proliferation to provide unique information for guiding patient treatment.     

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose

PURPOSE: To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS: Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS: Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION: PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.     

Detection of response to chemotherapy using positron emission tomography in patients with oesophageal and gastric cancer

BACKGROUND: The aim of the study was to determine whether 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) could detect response to chemotherapy in patients with oesophageal and gastric cancer. METHODS: Fourteen patients underwent imaging before and after chemotherapy using FDG-PET. Computed tomography (CT), dysphagia scores and weight changes were used for comparison of evidence of response. Tumour to liver ratios (TLRs) and influx constants for FDG (K) were used for quantification purposes. RESULTS: Thirteen of 14 lesions were successfully imaged before therapy. Changes were seen in all follow-up scans, ranging from a complete response to a 15 per cent increase in tumour FDG uptake. Response was demonstrated by CT in four patients; all four had large reductions in FDG uptake after chemotherapy. Two patients with an increase in FDG uptake reported no improvement in dysphagia and continued to lose weight during therapy. CONCLUSION: Changes in tumour FDG uptake were seen in all tumours after chemotherapy. FDG-PET may have a role to play in the assessment of patients with upper gastrointestinal malignancy receiving chemotherapy.     

Detection of oral dysplasia in animals with fluorine-18-FDG and carbon-11-tyrosine

The uptake of 18F-fluorodeoxyglucose (FDG) and L-[1-(11)C]tyrosine (TYR) was investigated in male Wistar albino rats with chemically induced dysplasia and oral squamous cell carcinoma (SCC) to correlate the uptake values with the grade of dysplasia. METHODS: The palates of 54 rats was painted three times per week with 4-nitroquinoline 1-oxide to create different stages of dysplasia and SCC. After 2, 4, 6, 8, 12, 16, 20, 26 and 30 wk, these rats were investigated with PET. Immediately thereafter, the rats were killed and histologically prepared. Standardized uptake values (SUVs) of the palate of the rats were calculated and correlated with the Epithelial Atypia Index (EAI) and the thickness of the epithelial layer. RESULTS: The TYR SUV correlated with the EAI and the epithelial thickness, 0.5 and 0.74, respectively. No correlation could be found for FDG SUV, compared to EAI and the epithelial thickness. CONCLUSION: For dysplasia and SCC, TYR showed higher uptake values than did FDG. It appeared that, for the detection of oral dysplasia, the tissue hyperplasia was more important than malignant features of dysplastic mucosa.     

18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma

BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) can be used to measure the glycolytic activity of tumor cells. Though the prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of patients with good prognoses may be discovered by determining the degree of FDG integration into tumors. METHODS: Fourteen patients with histologically proven pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or = 3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly different in terms of age, tumor location and size, staging, and treatment. However, analysis by the Kaplan-Meier method revealed that the groups had different prognoses (log rank test, P < 0.05). The mean survival of patients with high SUV was 5 months, whereas that of patients with low SUV was 14 months. There were not strong correlations between the SUVs and tumor size (0.56), serum carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52). CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor for patients with pancreatic adenocarcinoma.     

Standardized uptake value and quantification of metabolism for breast cancer imaging with FDG and L-[1-11C]tyrosine PET

The aims of the study were to compare the value of L-[1-11C]tyrosine (TYR) and [IBF]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. METHODS: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. RESULTS: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG. Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). CONCLUSION: In this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease. SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.     

Tumor cell spheroids as a model for evaluation of metabolic changes after irradiation

Tumor cell spheroids provide a good model to evaluate the relationship between tumor volume and the number of viable cells in the volume with the uptake of metabolic tracers before and after therapy. They represent the only in vitro model that allows the determination of the activity per unit volume, a parameter which is relevant for interpretation of PET studies. The purpose of this study was to evaluate this model with respect to the uptake of 14C-FDG, 3H-methionine and 3H-thymidine with and without exposure to irradiation. METHODS: Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media containing 14C-FDG, 3H-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 and 48 hr after exposure to a single radiation dose of 6 Gy together with control spheroids. Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable cells and cpm/0.01 mm3. In addition, the proliferative capacity of control and irradiated spheroids was determined using the clonogenic assay. RESULTS: Spheroid uptake of FDG decreased with time after irradiation, while the uptake per 1000 viable cells was increased significantly. The activity per unit volume remained unchanged in comparison to control spheroids. Methionine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 viable cells. Uptake per unit volume also remained unchanged in comparison to controls. Thymidine uptake per 1000 viable cells did not change after irradiation but showed significant differences in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitable fraction containing DNA was 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after therapy recovered with the increase in thymidine uptake and with the increase in thymidine incorporation into DNA. CONCLUSION: The results show that the activity determined within a certain tumor volume is a balance between the increased tracer uptake by surviving cells after therapy and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged activity per unit volume within the spheroid, as found for FDG and methionine, may not fully reflect therapy-induced metabolic changes in tumors.     

F-18 FDG whole-body positron emission tomography scan in primary breast sarcoma

Three patients with primary breast sarcoma showed intense F-18 FDG breast uptake on the whole-body scan. In two patients the uptake was irregular and associated with cold foci that corresponded to hypodense lesions noted on the chest CT; these represented areas of pathologically demonstrated tumor necrosis. There was also intense FDG uptake in pulmonary, axillary, and supraclavicular lymph node metastases. All lesions were confirmed by CT scan of the chest. Thus F-18 FDG positron emission tomographic scanning accurately staged the tumors in these two patients, and it documented local recurrence in the third patient. Histopathologic examination showed evidence of a high-grade sarcoma, a primary rhabdomyosarcoma, and a malignant cystosarcoma phyllodes of the breast. Similar to breast carcinoma, F-18 FDG whole-body positron emission tomographic imaging could be useful in diagnosing and staging primary breast sarcomas.     

Kinetic analysis of glucose metabolism by FDG-PET versus proliferation index of Ki-67 in meningiomas--comparison with gliomas

I compared glucose metabolism by 18F-fluorodeoxy-glucose (FDG)-PET with proliferative potentials determined by using Ki-67 in meningiomas and gliomas. Ki-67 labeling index (LI) as proliferation index was used to assess tumor aggressiveness. In FDG-PET, I measured tumor versus contralateral gray matter ratio (T/N), standardized uptake value (SUV), kinetic rate constants (k1, k2, k3) which were analyzed according to the three compartment FDG model, and kinetic cerebral metabolic rate of glucose (kCMRGl). Significantly elevated FDG uptake in T/N, kCMRGl was found in a high Ki-67 LI (above 2%) group compared to a low Ki-67 LI group in gliomas, but there was not found significant difference between these two groups in meningiomas. Tumor k3 value, an indicator of hexokinase activity, of a high Ki-67 LI group was significantly higher than that of a low Ki-67 LI group. It was found that k3 correlated with Ki-67 LI. The k3 value is useful for estimating the biological aggressiveness of meningiomas.     

Genetic analysis of protein C deficiency in nineteen Japanese families: five recurrent defects can explain half of the deficiencies

OBJECTIVE: The lack of sensitivity and specificity of conventional imaging techniques based on morphological critera is responsible for considerable limitations in the staging and surveillance of oral cancer. Therefore, this study investigates the contribution of [F18]-2-fluordesoxyglucose (FDG) positron emission tomography (PET) to tumor management with special regard to lymphnode involvement and therapeutic monitoring after radiotherapy. DESIGN: Prospective observational study. PATIENTS: Twenty-one patients with advanced oral cancer, predominantly T3/T4. INTERVENTION: FDG-PET scans before and after preoperative radio(chemo)therapy. Standardized uptake values (SUV) were determined for the tumor site and lymphnode areas. PET scans were correlated to histological findings after ablative tumor surgery. RESULTS: FDG-PET yielded superior sensitivity and specificity for tumor and lymphnode assessment. The effect of radiotherapy was reflected by the metabolic activity of the tumor, which shows a close correlation between the decrease of FDG uptake and histologic tumor regression. PET detected distant metastases and simultaneous tumors. CONCLUSION: FDG-PET is a challenging imaging technique with the potential to improve staging procedures for oral cancer. In the monitoring of metabolic activity of the tumor in the course of radio(chemo)therapy, FDG-PET allows objective measurement of the treatment response.