Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.     

Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer

The aim of this prospective study was to investigate if high uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) is associated with aggressiveness in head and neck cancer and low probability of survival. METHODS: Thirty-seven patients with squamous-cell carcinoma of the head and neck underwent FDG-PET in the fasting state before cancer treatment. FDG uptake in primary tumor was quantitated as the standardized uptake value of FDG normalized to the predicted lean body mass (SUVlean, n = 37) and as the graphically determined metabolic rate for FDG (rMR[FDG], n = 34). Paraffin-embedded tumor samples were used for histologic evaluation, and expression of cytokeratin and Ki-67 antigen were assessed by immunohistochemistry. RESULTS: Interobserver agreement for the determination of quantitative uptake of FDG in tumors was excellent (r2 = 0.996, p < 0.00001), and all 37 primary tumors were visualized. A high uptake of FDG as assessed by SUVlean was associated with a higher than the median mitotic count (p = 0.01), absence of keratinization (p = 0.03), low or moderate histological grade of differentiation (p = 0.046) and advanced stage (p = 0.03), but not with Ki-67 expression (p = 0.11). The overall survival of patients with a SUVlean lower than or equal to the median value (9.0) was clearly better in univariate analysis than that of patients with a SUVlean higher than the median (3-yr survival 73% versus 22%, relative risk of death (RR) 4.2, 1.6-11.0). However, in a multivariate analysis the only independent predictors of survival were the mitotic count (RR 4.0, 1.4-11.7) and stage (3.8, 1.2-12.2). CONCLUSION: High uptake of FDG in untreated head and neck cancer is associated with advanced disease, and may portend poor survival. Aggressive treatment approaches should be considered for patients presenting with a tumor with high uptake of FDG.     

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.     

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   

Coregistration of FDG PET and MRI of the head and neck using normal distribution of FDG

For better localization of head and neck structures by PET with 2-(18)F-2-deoxy-D-glucose (FDG), direct incorporation of anatomical information from MRI by the coregistration of FDG PET and MRI without external markers is proposed. METHODS: Seventeen patients with neoplasms and 16 normal subjects who had both FDG PET and MRI were studied. First, the three-dimensional normal distribution of FDG was evaluated, and then the structures of the head and neck regions with normal distribution patterns of FDG were used as internal markers for the coregistration of PET and MRI. The effectiveness of the coregistration was evaluated using focal neoplasms that were identified by both PET and MRI as fiducial internal markers. RESULTS: The normal structures selected as internal landmarks for coregistration were the tonsils, salivary glands, mucosal layers of the oral cavity and pharynx, spinal cord, inferior portion of the frontal lobe, cerebellum and nasal turbinates. These structures were more easily observed in sagittal or coronal sections than in transaxial sections. All primary neoplasms were delineated by PET, whereas 4 were missed by MRI. Thirteen primary tumors and 7 cervical lymph node metastases coregistered well, with a center-of-mass distance of <2 mm, whereas 10 lymph node metastases were slightly misregistered, with a center-of-mass distance of 7.8+/-6.5 mm (mean+/-s.d.), probably due to differences in neck positions. CONCLUSION: Normal distribution of FDG uptake in the head and neck regions delineated by multidirectional sections is important for effective coregistration of FDG PET with MRI.     

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.     

Posterior traumatic dislocation of a Thompson prosthesis: report of a case

Fluorine-18-fluorodeoxyglucose (F-18 FDG) PET was used to evaluate early-stage larynx cancer before and after radiotherapy. Less radical salvage surgery might be possible after timely diagnosis of recurrent or persistent tumor after radiotherapy. Eight patients with early-stage laryngeal cancer (two carcinoma in situ; six stage T1: tumor limited to vocal cords with normal mobility) underwent irradiation for potential cure. Five patients had pre- and postradiotherapy F-18 FDG PET, and three had postradiotherapy F-18 FDG PET only. All patients underwent a CT scan of the neck at the time of the F-18 FDG PET scan. One patient had a positive result of postradiotherapy F-18 FDG PET but a negative result of a CT of the neck, and biopsy revealed recurrent squamous carcinoma. Seven patients who had negative results of postradiotherapy F-18 FDG PET were free of disease at the 15-month median follow-up evaluation. (Three of them had no cancer on biopsy of the larynx, and four others were followed with periodic endoscopic examinations that revealed complete disappearance of the tumor.) F-18 FDG PET scan may be useful for earlier diagnosis of recurrent or persistent laryngeal cancer after radiotherapy and is preferable to repeated biopsies, which would traumatize radiation-damaged tissues. A prompt early diagnosis of failure of radiotherapy will lead to less radical salvage surgery.     

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.     

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.     

Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions

PURPOSE: 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is currently the method of choice for the detection of bone metastases, but 18F-fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior spatial resolution and improved sensitivity. We have compared 18FDG PET with 99mTc MDP bone scintigraphy in patients with skeletal metastases from breast cancer and have analyzed the data in subgroups based on radiographic characteristics of lesions. PATIENTS AND METHODS: Twenty-three women with breast cancer and confirmed bone metastases were studied with both 99mTC MDP bone scintigraphy and 18FDG PET, and the number of lesions detected and the quantitation of uptake (standardized uptake values [SUVs]) of 18FDG in osteolytic and osteoblastic metastases were compared. Survival was compared for both lytic and blastic bone metastases and for patients with high and low accumulation of 18FDG. RESULTS: 18FDG PET detected more lesions than 99mTc MDP scintigraphy (mean, 14.1 and 7.8 lesions, respectively; P < .01). However, 18FDG detected fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of patients with osteoblastic disease (P < .05). Higher SUVs were observed for osteolytic than osteoblastic disease (mean, 6.77 and 0.95, respectively; P < .01). Survival was lower in patients with osteolytic disease compared with the remainder (P=.01). A difference in survival was not found for those patients with high SUVs (> 3.6; P=.4). CONCLUSION: 18FDG PET is superior to bone scintigraphy in the detection of osteolytic breast cancer metastases, which led to a poorer prognosis. In contrast, osteoblastic metastases show lower metabolic activity and are frequently undetectable by PET. The biologic explanation for this observation remains to be elucidated.     

Positron emission tomography (PET) and (F-18)-fluorodeoxyglucose in (FDG) in cancerology

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a scintigraphic imaging technique undergoing a rapid growth in the field of oncology. The constant progress of the detectors, either CDET or PET dedicated cameras, allows to obtain in routine conditions images with a 5 mm spatial resolution. Absolute tracer uptake quantification is also possible, which allows to evaluate objectively therapy efficacy. The mechanisms of FDG tissular accumulation are now better understood. Increase of glycolysis and of transmembrane transport of glucose seems to be at the origin of the high tumorous accumulation of FDG. The main current oncologic application of FDG PET is the diagnosis of malignancy of the isolated pulmonary nodules, with a sensitivity of more than 95%, and in the staging of lung cancer where PET shows higher performances than conventional imaging. The same stands in cutaneous melanoma and for malignancies of the digestive tract, either in colorectal, pancreatic or esophageal localizations. In colorectal cancers, the role of PET has for long being recognized in the differential diagnosis between recurrence and postoperative fibrosis. In the head and neck tumors, FDG also allows to differentiate between recurrence and postradiation necrosis. In lymphoma, the most suitable site for biopsy can be identified on a PET scan and therapy efficacy can also be assessed. In breast cancer, the detection of metastases seems to be possible with FDG. In brain and thyroid cancers, the role of FDG PET remains to be further determined. The low uptake of FDG in prostate cancer metastasis is not in favor of its use in this indication. In conclusion, the indications of FDG PET in oncology are now becoming more precise and it can be expected that clinical PET centers will soon appear in France.     

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.     

Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methionine

PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-11C-methionine (11C-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, 11C-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and 11C-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with 11C-methionine outlined the tumors as areas of increased accumulation of 11C-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with 11C-methionine can play complementary roles in the evaluation of brain tumors.     

Pulmonary fibrosis correlates with duration of tissue neutrophil activation

The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metabolic activity of neutrophils with positron emission tomography (PET) to measure regional uptake of (18F)-2-fluoro-2-deoxy-D-glucose (18FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the 18FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (Tmax) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (Tmax), 0.045 +/- 0.030 h-1 (k); Streptococcus pneumoniae 15 h, 0.068 +/- 0.012 h-1; bleomycin 28 h, 0.002 +/- 0.001 h-1; microcrystalline silica (microXSiO2), 90 h, 0.0012 +/- 0.0007 h-1; amorphous silica (aSiO2), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO2 was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and microXSiO2 persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the 18FDG signal following C5a and S. pneumoniae, but not bleomycin and microXSiO2. Autoradiography of lungs following administration of (3H)-deoxyglucose [(3H)-DG] showed specific localization to neutrophils in all models. Thus, 18FDG uptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to persistence of this activity.     

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.     

Detection of extrathoracic metastases by positron emission tomography in lung cancer

BACKGROUND: Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. METHODS: One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. RESULTS: Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. CONCLUSIONS: Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.     

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.     

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.     

Carbon-11-thymidine and FDG to measure therapy response

This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.     

Dual isotope F-18 FDG and Tc-99m RBC imaging for lung cancer

PURPOSE: To produce fluorodeoxyglucose (FDG) images with markers for normal organs and large blood vessels in patients with suspected lung cancer. METHODS: Dual isotope SPECT images were made using F-18 FDG- and Tc-99m-labeled autologous red cells. RESULTS: FDG-positive lesions are localized in relation to major structures when they are viewed in a fused rotating three-dimensional display or in cross sections. CONCLUSIONS: Tc-99m red cell and FDG fusion imaging provides relative location information for lung tumors.