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.

Resistance to the tyrosine kinase inhibitor axitinib is associated with increased glucose metabolism in pancreatic adenocarcinoma.

Alterations in energy (glucose) metabolism are key events in the development and progression of cancer. In pancreatic adenocarcinoma (PDAC) cells, we investigated changes in glucose metabolism induced by resistance to the receptor tyrosine kinase inhibitor (RTKI) axitinib. Here, we show that human cell lines and mouse PDAC cell lines obtained from the spontaneous pancreatic cancer mouse model (Kras(G12D)Pdx1-cre) were sensitive to axitinib. The anti-proliferative effect was due to a G2/M block resulting in loss of 70-75% cell viability in the most sensitive PDAC cell line. However, a surviving sub-population showed a 2- to 3-fold increase in [C-14]deoxyglucose ([C-14]DG) uptake. This was sustained in axitinib-resistant cell lines, which were derived from parental PDAC. In addition to the axitinib-induced increase in [C-14]DG uptake, we observed a translocation of glucose transporter-1 (Glut-1) transporters from cytosolic pools to the cell surface membrane and a 2-fold increase in glycolysis rates measured by the extracellular acidification rate (ECAR). We demonstrated an axitinib-induced increase in phosphorylated Protein Kinase B (pAkt) and by blocking pAkt with a phosphatidylinositol-3 kinase (PI3K) inhibitor we reversed the Glut-1 translocation and restored sensitivity to axitinib treatment. Combination treatment with both axitinib and Akt inhibitor in parental pancreatic cell line resulted in a decrease in cell viability beyond that conferred by single therapy alone. Our study shows that PDAC resistance to axitinib results in increased glucose metabolism mediated by activated Akt. Combining axitinib and an Akt inhibitor may improve treatment in PDAC.

Recurrent and metastatic breast cancer PET, PET/CT, PET/MRI: FDG and new biomarkers.

Primary breast cancer often displays only moderately increased glucose metabolism resulting in a low sensitivity of positron emission tomography (PET) using [F-18]fluorodeoxyglucose (FDG) in detecting small breast carcinomas, locoregional micrometastases and non-enlarged tumor infiltrated lymphnodes. In contrast, distant breast cancer metastases are generally characterized by significantly increased metabolic activity compared to normal tissue. Therefore, FDG-PET provides accurate diagnostic information as a whole body imaging modality in staging of breast cancer patients. The metabolic information from FDG-PET/CT is often more sensitive than conventional imaging for the detection of distant metastases, particularly in the recurrent setting. FDG-PET is superior in detecting tumor-involved distant lymphnodes, particularly those which are normal in size, as well as in characterizing enlarged lymphnodes as positive or negative for malignancy. Of note, CT is superior in detecting small lung metastases. Although the overall sensitivity for bone scintigraphy and FDG-PET are comparable, bone scintigraphy seems to be superior in the detection of osteoblastic disease whereas FDG-PET is superior for osteolytic metastases, suggesting a complementary role for both imaging procedures. FDG-PET/MR has an evolving role in breast cancer management, for example in the detection of liver metastases and in the research setting for treatment monitoring. The utilization of PET for prediction of treatment response to primary chemotherapy is an area of active research, using FDG as well as other PET biomarkers including [F-18]Fluoroestradiol, [F-18]Fluorothymidine and integrin targeting tracer for monitoring anti-angiogenic therapy.

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.

Positron emission tomography for the diagnosis of breast cancer.

This article reviews the literature on breast imaging with [18F]fluorodeoxyglucose positron emission tomography (FDG PET). In clinical applications, there is currently no defined role for detecting primary breast cancer. The limited sensitivity of FDG PET does not allow the exclusion of malignancy, in particular small breast carcinomas, micrometastases and small, tumour infiltrated lymph nodes. However, in advanced stages, PET accurately determines the extent of disease, including the loco-regional lymph node status. Furthermore, whole-body PET imaging promises a high diagnostic accuracy for detecting recurrent or metastatic breast carcinoma. Future clinical applications may include monitoring therapeutic effects.

Diagnosis and monitoring of urological tumors using positron emission tomography.

The purpose of this article was to critically review the diagnostic value of positron emission tomography (PET) in urological oncology. Urinary tract tumor assessment is hampered by the renal elimination of (18)F-fluorodeoxyglucose (FDG), the most commonly used PET radiopharmaceutical. PET imaging offers no significant benefits over conventional imaging modalities for renal cell and bladder carcinomas. As a result of the low metabolic activity of prostate cancer, PET does not differentiate adequately between adenoma and carcinoma, nor detect local recurrence after radical prostatectomy with sufficient sensitivity. However, lymph node staging with FDG-PET, specifically in bladder cancer, has been shown to have a potential clinical benefit. Further studies are required to determine the clinical value of retroperitoneal lymph node staging and recurrent disease detection in germ cell tumors. Finally, encouraging early results exist for the use of serial PET measurements to predict and assess therapy response to chemotherapy which may also be valuable in urological oncology.

Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression.

Various radiotracers based on uracil nucleosides (e.g. [124I]2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil, [124I]FIAU) and acycloguanosine derivatives (e.g. [18F]9-[(3-fluoro-1-hydroxy-2-propoxy) methyl] guanine, [18F]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression. However, these radiotracers have been evaluated in different in vitro and in vivo models, precluding a direct comparison. Therefore, we directly compared [18F]FHPG and radioiodinated FIAU to assess their potential for PET imaging of transgene expression. The uptake of [125I]FIAU, [18F]FHPG and [3H]acyclovir was determined in vitro using four different HSV1-tk expressing cell lines and their respective negative controls. The in vitro tracer uptake was generally low in non-transduced parental cell lines. In HSV1-tk expressing cells, [3H]acyclovir showed approximately a twofold higher tracer accumulation, the [18F]FHPG uptake increased by about sixfold and the [125I]FIAU accumulation increased by about 28-fold after 120-min incubation of T1115 human glioblastoma cells. Similar results were found in the other cell lines. In addition, biodistribution and positron emission tomography (PET) studies with [18F]FHPG and [124/125I]FIAU were carried out in tumour-bearing BALB/c mice. Significantly higher specific accumulation of radioactivity was found for [125I]FIAU compared with [18F]FHPG. The ratio of specific tracer accumulation between [125I]FIAU and [18F]FHPG increased from 21 (30 min p.i.) to 119 (4 h p.i.). PET imaging, using [124I]FIAU, clearly visualised and delineated HSV1-tk expressing tumours, whereas only a negligible uptake of [18F]FHPG was observed. This study demonstrated that in vitro and in vivo, the radioiodinated uracil nucleoside FIAU has a significantly higher specific accumulation than the acycloguanosine derivative [18F]FHPG. This suggests that [124I]FIAU should be the preferred reporter probe for PET imaging of HSV1-tk gene expression. Thus, further attempts to develop suitable PET tracers for the assessment of HSV1-tk gene expression should also focus on 18F-labelled uracil derivatives.

Pitfalls in imaging Hodgkin's disease with computed tomography and positron emission tomography using fluorine-18-fluorodeoxyglucose.

We report on a patient with Hodgkin's disease who presented with hypodense splenic lesions and corresponding increased glucose metabolism in FDG-PET imaging, four months after completion of initial treatment, suggestive of early relapse. Serological testing for toxoplasma gondii, however, showed evidence of a recently reactivated or newly acquired infection. Three weeks after immediate antibiotic treatment with Daraprime and Sulfadiazin, the splenic lesions had completely resolved. Additionally, serological titers for toxoplasma gondii were normalized and whole body FDG-PET imaging showed no metabolic activity. Although the positive predictive value of PET imaging to indicate lymphoma is reported to be higher than CT, hypermetabolic lesions are not specific for malignant tissue. Whereas benign tumors typically show low glucose metabolism, activated granulocytes and macrophages may display significantly increased glucose consumption. In conclusion, our case report shows that although therapeutic decisions are often based on the results of imaging modalities, the taking of a detailed history and the acquisition of histological confirmation of the suspected lymphoma relapse are also advisable where possible. Cellular immunodeficiency can result in severe infections even in patients with intermediate stage Hodgkin's lymphoma in remission after combined modality treatment. Therefore, despite the high sensitivity of FDG-PET imaging for the detection of recurrent lymphoma, the differential diagnosis of infectious lesions should be kept in mind, in particular in immunocompromised patients.

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.

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.

Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography.

OBJECTIVE: To evaluate the use of positron emission tomography using [(18)F]-fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy and chemotherapy in patients with locally advanced esophageal cancer. SUMMARY BACKGROUND DATA: Imaging modalities, including endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging, currently used to evaluate response to neoadjuvant treatment in esophageal cancer do not reliably differentiate between responders and nonresponders. METHODS: Twenty-seven patients with histopathologically proven squamous cell carcinoma of the esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant therapy consisting of external-beam radiotherapy and 5-fluorouracil as a continuous infusion. FDG-PET was performed before and 3 weeks after the end of radiotherapy and chemotherapy (before surgery). Quantitative measurements of tumor FDG uptake were correlated with histopathologic response and patient survival. RESULTS: After neoadjuvant therapy, 24 patients underwent surgery. Histopathologic evaluation revealed less than 10% viable tumor cells in 13 patients (responders) and more than 10% viable tumor cells in 11 patients (nonresponders). In responders, FDG uptake decreased by 72% +/- 11%; in nonresponders, it decreased by only 42% +/- 22%. At a threshold of 52% decrease of FDG uptake compared with baseline, sensitivity to detect response was 100%, with a corresponding specificity of 55%. The positive and negative predictive values were 72% and 100%. Nonresponders to PET scanning had a significantly worse survival after resection than responders. CONCLUSION: FDG-PET is a valuable tool for the noninvasive assessment of histopathologic tumor response after neoadjuvant radiotherapy and chemotherapy.

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.

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.

Preoperative evaluation of pancreatic masses with positron emission tomography using 18F-fluorodeoxyglucose: diagnostic limitations.

Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue 18F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n = 38) or follow-up (n = 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.

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.

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.

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.