The role of FDG-PET and bone marrow examination in lymphoma staging.

The introduction of positron emission tomography using [F-18]fluorodeoxyglucose (FDG-PET) has had a substantial impact on the management of patients with lymphoma. Increasing numbers of patients are having an FDG-PET study as part of their initial staging, despite FDG-PET cannot be considered yet a standard procedure for staging in many types of lymphoma. FDG-PET has demonstrated its superiority over conventional imaging to identify nodal and extra-nodal sites of disease and provides complementary information to that obtained with bone marrow biopsy. This can result in disparities in the staging and prognostication of patients based on the procedures used to assess the extension of the disease. The difficulty lies in how to use the information provided by FDG-PET to communicate effectively when using staging classifications and prognostic indices that were designed following conventional imaging.

Assessment of residual tumour by FDG-PET: conventional imaging and clinical examination following primary chemotherapy of large and locally advanced breast cancer.

BACKGROUND: The aim of this was to evaluate FDG-PET (2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography) for assessment of residual tumour after primary chemotherapy of large and locally advanced breast cancer in comparison with conventional imaging modalities. METHODS: In a prospective multicentre trial, 99 patients underwent one or more breast imaging modalities before surgery in addition to clinical examination, namely, FDG-PET (n=89), mammography (n=47), ultrasound (n=46), and magnetic resonance imaging (MRI) (n=46). The presence of residual tumour by conventional imaging, dichotomised as positive or negative, and the level of FDG uptake (standardised uptake values, SUV) were compared with histopathology, which served as the reference standard. Patients with no residual tumour or only small microscopic foci of residual tumour were classified as having minimal residual disease and those with extensive microscopic and macroscopic residual tumour tissue were classified as having gross residual disease. RESULTS: By applying a threshold SUV of 2.0, the sensitivity of FDG-PET for residual tumour was 32.9% (specificity, 87.5%) and increased to 57.5% (specificity, 62.5%) at a threshold SUV of 1.5. Conventional imaging modalities were more sensitive in identifying residual tumour, but had a low corresponding specificity; sensitivity and specificity were as follows: MRI 97.6 and 40.0%, mammography 92.5 and 57.1%, ultrasound 92.0 and 37.5%, respectively. Breast MRI provided the highest accuracy (91.3%), whereas FDG-PET had the lowest accuracy (42.7%). CONCLUSIONS: FDG-PET does not provide an accurate assessment of residual tumour after primary chemotherapy of breast cancer. Magnetic resonance imaging offers the highest sensitivity, but all imaging modalities have distinct limitations in the assessment of residual tumour tissue when compared with histopathology.

Radioisotopic localization of (90)Yttrium-ibritumomab tiuxetan in patients with CD20+ non-Hodgkin's lymphoma.

PURPOSE: (90)Yttrium-ibritumomab-tiuxetan (Zevalin) is an effective treatment for relapsed or refractory low-grade, follicular, or transformed B-cell NHL. The purpose of this study is to assess whether tissue and cellular localization of (90)Y-ibritumomab-tiuxetan determined by autoradiography and radioactivity localized to tumor tissue might enhance our understanding of the mechanism of action of radioimmunotherapy. METHODS: Eight eligible patients had CD20+ NHL, a bulky peripheral lymph node, and were scheduled for (90)Y-ibritumomab-tiuxetan treatment. 2-Deoxy-2-[F-18]fluoro-D: -glucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed prior to treatment and at 12 weeks after therapy for assessment of response. Bone marrow, lymph node, and blood samples were collected 114 +/- 3 h after 14.8 MBq/kg (90)Y-ibritumomab-tiuxetan and processed for histology, scintillation counting, and microscopic autoradiography. RESULTS: Pericellular membrane localization of (90)Y-ibritumomab-tiuxetan to lymphoma cells was observed by autoradiography in the involved areas of lymph node with absence of significant localization in histologically normal sections of bone marrow. Pericellular radioactivity and the highest quantitative radioactivity were observed in lymph node samples of responding patients. CONCLUSIONS: (90)Y-ibritumomab-tiuxetan localizes to the surface membrane of CD20+ lymphoma cells in affected lymph nodes. The patients with the highest quantitative concentration of radioactivity to the lymph node as determined by scintillation counting were observed to have a clinical and FDG-PET/CT response.

Comparison between positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose, conventional imaging and computed tomography for staging of breast cancer.

BACKGROUND: The presence, extent and localization of distant metastases are key prognostic factors in breast cancer patients and play a central role in therapeutic decision making. The aim of this study was to compare the diagnostic performance of positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) with that of computed tomography (CT) and conventional imaging including chest radiography, abdominal ultrasound and bone scintigraphy. PATIENTS AND METHODS: A total of 119 consecutive patients with newly diagnosed locally advanced disease (n = 69) or previous history of breast cancer (n = 50) who had clinical suspicion of metastatic disease underwent FDG-PET, CT and conventional imaging procedures. Imaging results were retrospectively compared with histopathology and clinical follow-up which served as a reference standard. RESULTS: FDG-PET detected distant metastases with a sensitivity of 87% and a specificity of 83%. In contrast, the sensitivity and specificity of combined conventional imaging procedures were 43% and 98%, respectively. CT revealed a sensitivity of 83% and a specificity of 85%. CONCLUSIONS: In breast cancer, FDG-PET is superior to conventional imaging procedures for detection of distant metastases. Although FDG-PET and CT provided similar diagnostic accuracy, the information was often found to be complementary. With increasing availability of FDG-PET/CT, prospective studies are needed to determine whether it could potentially replace the array of conventional imaging procedures used today.

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.

Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography.

We report a series of studies that assess the feasibility and sensitivity of imaging of herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression with [124I]-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV1-tk gene expression. Studies were performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral-mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild-type W256 tumor in each animal was accomplished by direct intratumoral injection of retroviral vector-producer cells (W256-->W256TK* tumors). Tumors produced from W256 and W256TK+ cells served as the negative and positive control in each animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in nontransduced wild-type W256 tumors. The level of "specific" incorporated radioactivity in transduced portions of both W256TK* and W256TK+ tumors was relatively constant between 4 and 50 h. In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate between different levels of HSV1-tk gene expression. Multiple s.c. tumors were produced from wild-type RG2 cells and stably transduced RG2TK cell lines that express different levels of HSV1-tk. A highly significant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation constant (Ki)] and an independent measure of HSV1-tk expression (sensitivity of the transduced tumor cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship was defined as a sensitivity index. We have demonstrated for the first time that highly specific noninvasive images of HSV1-tk expression in experimental animal tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system. The ability to image the location (distribution) of gene expression and the level of expression over time provides new and useful information for monitoring clinical gene therapy protocols in the future.

FDG-PET imaging in hematological malignancies.

The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques.

Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: the cellular basis for cardiac gene imaging.

BACKGROUND: Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue. METHODS AND RESULTS: The combination of the herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [(14)C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained <15% of positive controls. Additionally, vectors were applied intramyocardially in Wistar rats. The marker substrate [(125)I]FIAU was injected intravenously 3 days later, and animals were killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3. 4+/-2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (<10% of positive controls). CONCLUSIONS: Using an adenoviral vector, HSV1-tk can be successfully expressed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabeled FIAU. The results suggest that imaging transgene expression in the heart is feasible and may be used to monitor gene therapy noninvasively.

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer.

PURPOSE: To address the role of positron emission tomography (PET) using [(18)F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard. RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P <.05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responders were correctly identified (sensitivity 100%, specificity 85%) by a standardized uptake value decrease below 55% of the baseline scan. At this threshold, histopathologic response could be predicted with an accuracy of 88% and 91% after the first and second courses of therapy, respectively. CONCLUSION: This study demonstrates that in patients with advanced breast cancer undergoing primary chemotherapy, FDG-PET differentiates responders from nonresponders early in the course of therapy. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive preoperative chemotherapy in responding patients.

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.

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer. PATIENTS AND METHODS: Preoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses. RESULTS: Breast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer. CONCLUSION: Partial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.

Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis.

UNLABELLED: Breast cancer is characterized by elevated glucose consumption resulting in increased uptake of 18F-FDG. However, tracer uptake varies considerably among tumors imaged with PET. This study compared histologic and immunohistochemical tissue analysis of breast carcinomas with preoperative FDG uptake assessed by PET to identify tumor characteristics that define the degree of tracer accumulation. METHODS: FDG uptake in breast tumors was quantified by calculating standardized uptake values (SUVs) corrected for partial-volume effect and normalized to blood glucose level at the time of tracer injection. The histologic sections of 50 invasive and 6 noninvasive breast carcinomas were analyzed for histologic type, microscopic tumor growth pattern, percentage of tumor cells, presence of inflammatory cells, density of blood vessels, histopathologic grading, tumor cell proliferation (mitotic rate and antibody binding of MIB-1), expression of estrogen and progesterone receptors, and expression of the glucose transporter protein Glut-1. RESULTS: A positive correlation was found between FDG uptake and histologic tumor type (ductal vs. lobular; P = 0.003), microscopic tumor growth pattern (nodular vs. diffuse; P = 0.007), and tumor cell proliferation (MIB-1; P = 0.009). Tumors with diffuse growth patterns had significantly lower SUVs compared with clearly defined tumors. A weak relationship was found between FDG uptake and the percentage of tumor cells (P = 0.06). Lower densities of blood vessels corresponded to higher FDG uptakes (P = 0.08). However, even significant correlations showed poor correlation coefficients. No relationship was found between FDG uptake and the following: tumor size; axillary lymph node status; percentage of necrotic, fibrotic, and cystic compounds; presence of inflammatory cells; steroid receptor status; and expression of Glut-1. CONCLUSION: Histologic and immunohistochemical tissue analysis was unable to sufficiently explain the variation of FDG uptake in breast cancer. The degree of metabolic changes after malignant transformation is most likely explained by a complex interaction between cellular energy demand and tumoral microenvironment. Therefore, FDG PET imaging may not be used to estimate tumor biologic behavior of breast cancer such as differentiation, histopathologic grading, cell proliferation, or axillary lymph node status.

Breast imaging with fluorine-18-FDG PET: quantitative image analysis.

UNLABELLED: This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG). METHODS: In a prospective study, 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET. A total of 97 breast tumors were evaluated by histology, including 46 benign and 51 malignant tumors. Using a whole-body PET scanner, attenuation-corrected images were acquired between 40 and 60 min after tracer injection. For Patlak analysis, dynamic data acquisition was obtained in 24 patients. To differentiate between benign and malignant breast tumors, receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest, standardized uptake values (corrected for partial volume effect, normalized to blood glucose, partial volume effect and blood glucose, using the lean body mass as well as the body surface area) and calculating the FDG influx rate (K) assessed by Patlak analysis. RESULTS: Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis. Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy. CONCLUSIONS: These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors. Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability.

Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging head and neck squamous-cell carcinomas.

UNLABELLED: Accurate, preoperative assessment of tumor extent and lymph node involvement is mandatory for individualized therapy in patients with squamous-cell carcinomas (SCCs) of the head and neck region. Metabolic imaging, [18F]fluorodeoxyglucose (FDG) PET and MRI were compared with postoperative, histologic tissue characterization. METHODS: Dynamic and static PET with 370 MBq [18F]FDG up to 60 min postinjection and MRI were compared prospectively in 22 patients with head and neck SCCs. PET results with and without attenuation correction were compared with postoperative T and N stages based on pathologic findings. RESULTS: Kinetic characteristics and tracer uptake intensity were similar in primary tumors and lymph node metastases. In both, FDG uptake did not reach a plateau phase 60 min postinjection. There was no statistically significant correlation of FDG uptake with plasma glucose level or histologic grading. All primary tumors were clearly demonstrated by PET, which tended to overestimate tumor size. The sensitivity and specificity for detecting individual lymph node involvement were 90% and 96%, respectively, for PET and, thus, significantly higher for MRI (78% and 71%, respectively; p < 0.05). N stages were correctly identified by MRI in only 4 patients; PET correctly staged lymph nodes in 15 of 17 patients. Based on "neck sides", the sensitivity and specificity were higher for PET, 89% and 100%, respectively, compared with MRI values of 72% and 56%, respectively. CONCLUSION: FDG-PET may be helpful in detecting occult primary tumors with positive lymph nodes.

FDG PET evaluation of granular cell tumor of the breast.

Granular cell tumor is a rare, usually benign neoplasm of neural origin that may arise in virtually any site and, when situated in the breast, can mimic breast carcinoma. We describe a case of granular cell tumor of the breast in a 57-yr-old woman. Clinical evaluation, mammography, sonography and MRI suggested a carcinoma with infiltration of skin and muscle. However, the tumor did not display increased glucose metabolism on PET. Clinical findings, imaging results, histological characteristics and surgical management are discussed.

Quantitative assessment of tumor metabolism using FDG-PET imaging.

Positron emission tomography using the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) provides a unique means of non-invasive assessment of tumor metabolism. Several approaches, of varying complexity, can be applied for quantitative image analysis. Previous studies have demonstrated that "standardized uptake values" (SUV) and simplified tracer kinetic modeling, using the "Patlak-Gjedde"-analysis, provide highly reproducible parameters of tumor glucose utilization. Quantification of regional FDG uptake gives complementary information to visual image interpretation and provides objective criteria for differentiation between benign and malignant lesions. Moreover, quantification of tumor glucose metabolism is essential for assessment of therapy induced changes. Clinical studies in breast cancer and lymphoma suggest that serial FDG-PET studies allow the prediction of response early in the course of chemotherapy. Therefore, FDG-PET may be helpful in patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose intense regimes. In addition, FDG-PET allows non-invasive assessment of tumor viability following chemo- and radiotherapy which permits individualized therapy management.

Detection of micrometastases in sentinel lymph nodes of the breast applying monoclonal antibodies AE1/AE3 to pancytokeratins.

Sentinel lymph node excision in breast cancer is a minimally invasive diagnostic procedure for accurate staging of the axilla and for avoiding unnecessary axillary dissection. In patients with palpable breast cancer we injected microcolloidal particles of human serum albumin labelled with technetium-99m the day before surgery. The sentinel node was detected intraoperatively with a handheld gammaprobe and then removed. Complete axillary dissection was performed and the nodes inspected by routine histological examination. The axillary lymph node status was correctly predicted by the sentinel node technique in 32 of 33 breast cancer patients. Two cases of micrometastases escaped routine histopathological detection but were identified by immunohistochemical analysis applying the antibody AE1/AE3 to pancytokeratins. Immunohistochemical examination of the sentinel node improves the diagnostic security of patients with breast carcinoma by detection of micrometastases.

Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer.

BACKGROUND: Sentinel lymphonodectomy is a new method for the classification of axillary lymph nodes in breast cancer. The optimum technique for the pathological examination of sentinel lymph nodes (SLNs) is still under debate. MATERIALS AND METHODS: Different histopathological techniques were evaluated in order to study their diagnostic accuracy regarding the detection of metastases in 49 SLNs of 40 breast cancer patients. RESULTS: In single hematoxylin and eosin (HE) stained paraffin sections 18 out of 40 patients showed positive SLNs and 8 out of 40 showed positive axillary lymph nodes (ALNs). Serial sections with a spacing of 150 microns between following sections revealed an additional 4 and 5 cases with positive SLNs and ALNs, respectively. Single HE frozen sections showed 11 tumor positive SLNs among 25 patients. The ultrarapid-immunohistochemistry on single frozen sections confirmed these data and detected one additional case with isolated tumor cells in the lymph node sinus. CONCLUSION: Histopathological nodal staging of SLNs should include serial sections with a spacing of 150 microns between sections as well as immunohistochemistry. The ultrarapid-immunohistochemistry is a sensitive method for the detection of minimal metastatic disease in SLNs and can be applied intraoperatively.

[Metabolic characterization of ovarian tumors with positron-emission tomography and F-18 fluorodeoxyglucose]. / Metabolische Charakterisierung von Ovarialtumoren mit der Positronen-Emissions-Tomographie und F-18-Fluordeoxyglukose.

PURPOSE: This study describes diagnostic accuracy of PET imaging in patients with ovarian tumours using histological diagnosis as gold standard. METHODS AND RESULTS: Pet studies were performed in 19 patients who were scheduled to undergo exploratory surgery for a suspicious ovarian mass and in 5 patients with suspected recurrence. The PET data were analyzed visually and quantitatively and compared to the histologic findings. 6 patients had ovarian cancer, while in 13 patients a benign tumour was found including inflammatory processes in 4 cases. All malignant tumours showed an enhanced FDG uptake with the exception of one false-negative borderline carcinoma. 4 cases with inflammatory processes as well as endometrial and follicular cysts revealed a high FDG uptake. A successful localisation of a recurrent tumour was possible in 4 out of 5 cases. Disseminated peritoneal carcinomatosis in two patients could not be detected by PET. CONCLUSIONS: Enhanced glucose metabolism of ovarian cancer enables PET diagnosis with a sensitivity of 83%. An intensive FDG uptake in inflammatory processes resulted in a specificity of only 54% in this study. The high sensitivity of PET for malignant tumours may be useful in the detection of recurrent ovarian cancer.