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Biomedical subjects

W A Weber

Publications and source records attributed to W A Weber.

At least 19 recordsLinked to original sources

FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding.

AIM: The incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. PATIENTS, METHODS: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. RESULTS: When read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of M1-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. CONCLUSION: About half of discordances between FDG PET and CT are clinically relevant. Concomitant reading of PET and CT is advisable as it reduces the overall rate of discordances and enhances the accuracy of PET in clinical relevant discordances (from 56% to 83%).

Adenocarcinoma↗

Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited data available, a standard imaging protocol for the prediction of tumour response has not yet been approved. The aim of this study was to compare commonly applied imaging protocols and calculations of the standardised uptake value (SUV) for the early prediction of histopathological response to chemotherapy. METHODS: Serial FDG PET scans of 43 patients with gastric carcinomas were retrospectively analysed. All patients received two consecutive scans (one bed position at 40 min p.i. and four bed positions at 90 min p.i.) at baseline and during the first cycle of cisplatinum-based chemotherapy. Reconstruction of the images was performed by filtered back-projection (FBP) and using an iterative algorithm (OSEM). SUVs were calculated with and without correction for the blood glucose level using normalisation by body weight, body surface area and lean body mass. Relative percentage changes between SUVs at baseline and follow-up were calculated and analysed for their potential to predict histopathological response to chemotherapy (ROC analysis). Response was defined as less than 10% viable tumour cells in the tumour specimen obtained by surgery 3-4 weeks after the completion of chemotherapy. RESULTS: Eight of 43 patients were histopathological responders to chemotherapy. The percentage changes in SUV(body weight) for responders and non-responders were -52.2 (+/-13.2) and -25.2 (+/-15.2), -54.7 (+/-18.2) and -24.5 (+/-16.1), -53.9 (+/-24.2) and -22.7 (+/-21.3), and -56.7 (+/-21.6) and -26.1 (+/-18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each case). According to ROC analysis, neither the scan protocol nor correction for blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off value (approx. -40% change in tumour SUV) for the prediction of response. Normalisation of SUVs by body surface area or lean body mass instead of body weight yielded essentially identical results. CONCLUSION: In gastric carcinomas the prediction of response to chemotherapy on the basis of relative tumour SUV changes is not essentially influenced by any of the methodological variations investigated (time delay after FDG administration, acquisition protocol, reconstruction algorithm, normalisation of SUV). This demonstrates the robustness of FDG PET for therapeutic monitoring and facilitates the comparability of studies obtained at different institutions and with different protocols. However, whichever method is used for therapy monitoring with FDG PET, a highly standardised protocol must be observed to take the dynamics of tumour FDG uptake into account.

Algorithms↗

Targeting of gelatinase activity with a radiolabeled cyclic HWGF peptide.

Matrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer as well as in numerous diseases. In this article, we describe the labeling of a phage display selected cyclic decapeptide containing the HWGF (histidine-tryptophane-glycine-phenylalanine) sequence to target MMP-2 and MMP-9. To evaluate the ability of this labeled peptide to monitor non invasively MMP-2 and MMP-9 activity, in vitro studies, biodistribution, competition studies and plasma metabolites analyses in Lewis Lung cancer tumor bearing mice were performed.

Animals↗

Radiotracer-based strategies to image angiogenesis.

Tumour-induced angiogenesis plays an important role in tumour progression. Great efforts are made to develop therapeutic strategies to interfere with this process resulting in the starvation of the tumour. However, strategies to monitor conventional therapies seems to be inappropriate to control these approaches. Thus, there is a keen interest in developing methods supplying information about the corresponding therapeutical effects. Several radiotracer-based approaches focused on different targets in the angiogenic process are currently investigated. One class of tracers is based on matrix metalloproteinases inhibitors. These compounds show promising results in in vitro assays. However, initial data from in vivo studies using murine tumour models could not confirm successful non-invasive monitoring of MMP activity yet. Another strategy uses a radiolabelled single chain fragment against the ED-B domain of fibronectin, an extracellular matrix protein. Promising results demonstrated selective accumulation of the tracer in the tumour vasculature of a murine tumour model. Most of the studies are concentrated on the development of radiolabelled antagonists of the integrin alpha(v)beta(3). This heterodimeric transmembrane glycoprotein is involved in the migration of activated endothelial cells during formation of new vessels. Different compounds have been labelled with (18F), (111)In, (99m)Tc, (90)Y and several iodine isotopes. In in vitro assays most of them revealed high alpha(v)beta(3) affinity and selectivity. Moreover, in different murine tumour models successful non-invasive determination of alpha(v)beta(3) expression has been shown. Some of these approaches indicate that tumour-induced angiogenesis can be monitored in animal studies. Nevertheless, translation of these approaches into clinical settings allowing visualisation of tumour-induced angiogenesis in patients needs still to be demonstrated.

Animals↗

[PET with (18)F-fluorodeoxyglucose for staging of non-small cell lung cancer].

AIMS: To evaluate studies on the use of positron emission tomography with the glucose analog (18)F-fluoro-deoxyglucose (FDG-PET) for the preoperative staging of patients with non-small cell lung cancer (NSCLC) according to the criteria of evidence based medicine and to discuss the cost-effectiveness of the technique. METHODS: Clinical studies published between 1995 and 2002 on the preoperative staging of non-small cell lung cancer were used for this analysis. Studies that did not meet the criteria published by the European Agency for the Evaluation of Medicinal Products (EMEA) were excluded. The validity of the studies was evaluated by a standardized rating system developed by the Agency for Health Care Policy and Research (AHCPR). RESULTS: For the detection of mediastinal lymph node metastases the mean sensitivity and specificity of FDG-PET on a patient basis is 85% and 87% (16 studies, 1355 patients). In studies that compared FDG-PET and computed tomography (CT) the mean sensitivity of CT was 66% at a specificity of 71%. In the detection of distant metastases FDG-PET correctly changed the tumor stage in 18% of the patients when compared to CT based staging (10 studies, 1073 patients). Five cost effectiveness analyses from the USA, Japan, and Germany concluded that FDG-PET improves the outcome of treatment at reduced or only slightly increased overall costs. Improvement of patient outcome was also demonstrated in a randomized trial, which found that the risk of a futile thoracotomy was reduced by 51% (p=0.003) when FDG-PET was added to the preoperative staging. CONCLUSION: According to the criteria of the AHCPR the use of FDG-PET for detection of mediastinal lymph node and distant metastases is documented at a level of evidence Ia and Ib, respectively. Since systematic analyses also indicate a favorable cost-effectiveness ratio FDG-PET has to be considered as "strictly indicated" for the preoperative staging of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Excretion of FDG into saliva and its significance for PET imaging.

AIM: Assessment of the salivary excretion of FDG and its significance during PET imaging. METHODS: Salivary samples from 16 patients were obtained during the first three hours after FDG injection and their activity concentrations were measured. Furthermore, regional FDG accumulations in whole body PET scans (60 min p.i., ROI technique) were determined in the following locations: vestibulum oris, floor of the mouth, hypopharynx, parotid gland, submandibular gland. This ROI analysis was repeated after drinking water (0.2 l) and a second scan (120 min p.i.). RESULTS: The salivary FDG concentrations (SUV) at the first, second and third hour p.i. were 0.2 +/- 0.1, 0.4 +/- 0.2, and 0.3 +/- 0.2, respectively. The FDG uptake in the investigated cranial and cervical sites ranged from SUV 1.2 +/- 0.5 in the major salivary glands to 2.1 +/- 0.5 in the floor of the mouth. These values remained unchanged after drinking of water. CONCLUSION: The salivary FDG concentration is higher than expected from the low physiologic content of glucose. This may--similarly to renal excretion--reflect a different behavior of FDG and glucose during reabsorption processes. Nevertheless, the salivary concentration of FDG is so low that no relevant influence on PET imaging is to be expected. Accordingly, the drinking of water prior to the scan is of no benefit for FDG PET imaging of the head and the neck.

Fluorodeoxyglucose F18↗

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.

Adenocarcinoma↗

Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography.

The alpha(v)beta3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the 18F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[18F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized alpha(v)beta3, alpha(v)beta5, and alpha(IIb)beta3 as well as in vivo studies using alpha(v)beta3-positive and -negative murine and xenotransplanted human tumors demonstrated receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios (e.g., 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the alpha(v)beta3 integrin status and therapy monitoring.

Animals↗

[Monitoring of response to neoadjuvant therapy by positron emission tomography (PET)].

Neoadjuvant therapy is frequently hampered by the lack of reliable non-invasive techniques for prediction and assessment of response. Positron emission tomography using the glucose analogue 18F-fluorodeoxyglucose (FDG-PET) provides a unique means of non-invasive assessment of tumor metabolism. Several recent studies have indicated that a reduction of tumor metabolic activity after neoadjuvant therapy is closely correlated with the degree of histopathological tumor regression. The reduction of metabolic activity may also allow one to predict subsequent response early during the course of therapy. Therefore FDG-PET may permit individualized therapy management. However, there is a requirement for larger-scale trials to assess this technique.

Female↗

Tumor angiogenesis targeting using imaging agents.

The inhibition of tumor induced angiogenesis is an emerging therapeutic strategy in clinical oncology aimed at halting cancer progression by suppressing tumor blood supply. As anti-angiogenic therapy is primarily cytostatic and not cytotoxic, the established criteria for assessing tumor response to chemo- and radiotherapy cannot be applied to anti-angiogenic therapy. Therefore, functional and molecular parameters for imaging of tumor angiogenesis are being intensively studied. Computed tomography, magnetic resonance imaging, ultrasound and scintigraphic techniques can assess changes in vascular permeability and tumor blood flow during anti-angiogenic therapy. Scintigraphic techniques, especially positron emission tomography (PET), may be used to monitor the consequences of anti-angiogenic therapy on tumor cell metabolism, proliferation and apoptosis. The high sensitivity of PET which allows measurements of tracer concentrations in the picomolar range is promising for the visualization of specific molecular targets prior to therapy thus identifying patients most likely benefit from a particular form of anti-angiogenic therapy.

Angiogenesis Inhibitors↗

Correlation between postoperative 3-[(123)I]iodo-L-alpha-methyltyrosine uptake and survival in patients with gliomas.

UNLABELLED: The aim of this study was to evaluate the prognostic value of SPECT imaging using the amino acid analog 3-[(123)I]iodo-L-alpha-methyltyrosine (IMT) in patients with gliomas. METHODS: One hundred fourteen consecutive patients with newly diagnosed gliomas were examined by IMT SPECT (low-grade glioma, n = 12; anaplastic astrocytoma or oligodendroglioma, n = 46; glioblastoma, n = 56). Seventy-one of these patients had undergone tumor resection 4-6 wk before SPECT imaging (group A). Forty-three patients with unresectable tumors were examined after stereotactic biopsy (group B). IMT uptake at the site of the tumor was assessed visually and quantified relative to a contralateral reference region (IMT uptake ratio). After IMT SPECT, all patients were treated with conformal radiotherapy. The median follow-up time was 27 mo. RESULTS: In group A, focal IMT uptake at the resection site was visible in 52 of 71 patients (73%). Median survival was only 13 mo in these patients, whereas median survival was reached in patients without focal IMT uptake (P = 0.02). Furthermore, the intensity of IMT uptake significantly correlated with survival: patients with an IMT uptake ratio > 1.7 were at a 4.6 times higher risk of death than were patients with a lower IMT uptake (P < 0.001). The IMT uptake ratio remained a significant prognostic factor when age and grading were included in a multivariate model. In contrast, IMT uptake did not correlate with survival in group B (P = 0.95). CONCLUSION: In patients with unresectable high-grade gliomas, IMT uptake appears not to correlate with the biologic aggressiveness of tumor cells. Nevertheless, the clear association between focal IMT uptake after tumor resection and poor survival suggests that IMT is a specific marker for residual tumor tissue. Therefore, IMT SPECT is expected to become a valuable tool for the planning and monitoring of local therapeutic modalities.

Adult↗

O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study.

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of L-[methyl-11C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1+/-0.2, 0.8+/-0.2 and 2.7+/-0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4+/-0.2, 0.9+/-0.1 and 3.3+/-1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0+/-0.1 SUV) was significantly lower than in tumour tissue (P = 0.007). For all lesions there was a close correlation (r = 0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions.

Adult↗

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.

Fluorodeoxyglucose F18↗

Effect of N-butylscopolamine on intestinal uptake of fluorine-18-fluorodeoxyglucose in PET imaging of the abdomen.

AIM: Circumscribed or diffuse intestinal uptake of F-18-fluorodeoxyglucose (FDG) is a frequent finding in PET imaging of the abdomen often interfering with correct scan interpretation. The aim of the present study was to determine whether the antiperistaltic agent N-butylscopolamine reduces intestinal FDG-uptake. METHODS: Whole body scans from 40 patients with malignant lymphoma and no evidence for intraabdominal tumor involvement were analyzed (6 bed positions; scan start 60 min post injection of approximately 350 MBq FDG; emission time 9 min per position; no attenuation correction). Twenty patients received 20 mg N-butylscopolamine in combination with an intravenous injection of FDG (test group) and 20 patients received only FDG (control group). For analysis, the intensity of bowel loops and diffuse abdominal background were compared to normal liver on a 4 point scale (0 = lowest intensity, 3 = highest) by two experienced nuclear medicine physicians. Furthermore, focal intestinal uptake was evaluated quantitatively by a ROI technique and bowel to liver ratios (b/l) were calculated. RESULTS: Bowel loops had lower intensity and occupied less abdominal regions in the test group than in the control group (visual score 1 vs. 1.5, p = 0.01; abdominal regions 1 of 5 vs. 2.5 of 5, p = 0.04). The visual score for diffuse abdominal background was 0.5 in the test group and 1 in the control group (p = 0.04). Bowel uptake interfered with scan interpretation in 1 of 20 patients in the test group and 6 of 20 patients in the control group (p = 0.01). The b/l ratios were 1.5 +/- 0.7 in the test group and 2.3 +/- 1.4 in the control group (p = 0.08). CONCLUSION: Administration of N-butylscopolamine reduces intestinal uptake of FDG and may facilitate accurate interpretation of abdominal FDG-PET studies.

Abdomen↗

Relevance of positron emission tomography (PET) in oncology.

BACKGROUND: The clinical use of positron emission tomography (PET) for detection and staging of malignant tumors is rapidly increasing. Furthermore, encouraging results for monitoring the effects of radio- and chemotherapy have been reported. METHODS: This review describes the technical principles of PET and the biological characteristics of tracers used in oncological research and patient studies. The results of clinical studies published in peer reviewed journals during the last 5 years are summarized and clinical indications for PET scans in various tumor types are discussed. RESULTS AND CONCLUSIONS: Numerous studies have documented the high diagnostic accuracy of PET studies using the glucose analogue F-18-fluordeoxyglucose (FDG-PET) for detection and staging of malignant tumors. In this field, FDG-PET has been particularly successful in lung cancer, colorectal cancer, malignant lymphoma and melanoma. Furthermore, FDG-PET has often proven to be superior to morphological imaging techniques for differentiation of tumor recurrence from scar tissue. Due to the high glucose utilization of normal gray matter radiolabeled amino-acids like C-11-methionine are superior to FDG for detection and delineation of brain tumors by PET. In the future, more specific markers of tumor cell proliferation and gene expression may allow the application of PET not only for diagnostic imaging also but for non-invasive biological characterization of malignant tumors and early monitoring of therapeutic interventions.

Carbon Radioisotopes↗

Imaging of lung cancer with fluorine-18 fluorodeoxyglucose: comparison of a dual-head gamma camera in coincidence mode with a full-ring positron emission tomography system.

Dual-head gamma cameras operated in coincidence mode are a new approach for tumour imaging using fluorine-18 fluorodeoxyglucose (FDG). The aim of this study was to assess the diagnostic accuracy of such a camera system in comparison with a full-ring positron emission tomography (PET) system in patients with lung cancer. Twenty-seven patients (1 female, 26 males, age 62+/-9 years) with lung cancer or indeterminate pulmonary nodules were studied on the same day with a full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system (ADAC Vertex MCD). Sixty minutes after injection of 185-370 MBq FDG, a scan of the chest was performed with the full-ring system. Approximately 2 h p.i., the coincidence camera study was performed. Coincidence gamma camera (CGC) and PET images with (PETac) and without attenuation correction (PETnac) were analysed independently by two blinded observers. In addition, FDG uptake in primary tumours and involved lymph nodes was quantified relative to normal contralateral lung (T/L ratios). All primary tumours were histologically proven. The lymph node status was histologically determined in 23 patients. In four patients, no lymph node sampling was performed because of extensive disease or concurrent illnesses. In the 27 patients, 25 primary lung cancers and two metastatic lesions were histologically diagnosed. The number of coincidences per centimetre axial field of view was 3.33+/-0. 93x10(5) for the CGC and 1.09+/-0.36x10(6) for the dedicated PET system. All primary tumours (size: 4.6+/-2.6 cm) were correctly identified in the CGC and dedicated PET studies. T/L ratios were 4. 7+/-2.5 for CGC and 6.9+/-2.8 for PETnac (P <0.001). Histopathological evaluation revealed lymph node metastases in 11 of 88 sampled lymph node stations (size: 2.3+/-1.0 cm). All lymph node metastases were identified in the PETac studies, while PETnac detected 10/11 and CGC 8/11. For positive lymph nodes that were visible in CGC and PETnac studies, T/L ratios were 3.7+/-2.3 for CGC and 6.6+/-3.1 for PETnac (P=0.02). The diameters of false-negative lymph nodes in the CGC studies were 0.75, 1.5 and 2 cm. False-positive FDG uptake in lymph nodes was found in two patients with all three imaging methods. For all lesions combined, T/L ratios in CGC relative to PETnac studies decreased significantly with decreasing lesion size (r=0.62; P<0.001). In conclusion, compared with a full-ring PET system the sensitivity of CGC imaging for detection of lung cancer is limited by a lower image contrast which deteriorates with decreasing lesion size. Nevertheless, the ability of CGC imaging to detect pulmonary lesions with a diameter of at least 2 cm appears to be similar to that of a full-ring system. Both systems provide a similar specificity for the evaluation of lymph node involvement.

Aged↗

Reproducibility of metabolic measurements in malignant tumors using FDG PET.

UNLABELLED: PET using 18F-fluorodeoxyglucose (FDG) is increasingly applied to monitor the response of malignant tumors to radiotherapy and chemotherapy. The aim of this study was to assess the reproducibility of serial FDG PET measurements to define objective criteria for the evaluation of treatment-induced changes. METHODS: Sixteen patients participating in phase I studies of novel antineoplastic compounds were examined twice by FDG PET within 10 d while they were receiving no therapy. Standardized uptake values (SUVs), FDG net influx constants (Ki), glucose normalized SUVs (SUV(gluc)) and influx constants (K(i,gluc)) were determined for 50 separate lesions. The precision of repeated measurements was determined on a lesion-by-lesion and a patient-by-patient basis. RESULTS: None of the parameters showed a significant increase or decrease at the two examinations. The differences of repeated measurements were approximately normally distributed for all parameters with an SD of the mean percentage difference of about 10%. The 95% normal ranges for spontaneous fluctuations of SUV, SUV(gluc), Ki and K(i,gluc) were determined to be +/-0.91, +/-1.14, +/-0.52 mL/100 g/min and +/-0.64 mL/100 g/min, respectively. Analysis on a lesion-by-lesion basis yielded similar results. CONCLUSION: FDG PET provides several highly reproducible quantitative parameters of tumor glucose metabolism. Changes of a parameter that are outside the 95% normal range determined in this study may be used to define a metabolic response to therapy.

Antineoplastic Agents↗

The value of F-18-fluorodeoxyglucose PET for the 3-D radiation treatment planning of malignant gliomas.

PURPOSE: The aim of the study was to determine the impact of positron emission tomography using the glucose analogue fluorine-18-fluorodeoxyglucose (FDG-PET) on the delineation of the target volume in three-dimensional radiation treatment planning of primary brain tumors. METHODS AND MATERIALS: In 18 patients with histologically proven (8x biopsy, 10x subtotal resection) primary brain tumors (8 astrocytomas grade III, one mixed glioma grade III, and 9 glioblastomas), magnetic resonance imaging (MRI) with gadolinium-DTPA and FDG-PET were performed in radiation treatment position within the same week. A computer program was developed for fusion of the PET and MR images. On corresponding axial slices, FDG uptake was compared to contrast enhancement in T1-weighted and to signal hyperintensity in T2-weighted MR images. Based on PET and MRI data, three-dimensional treatment planning was performed. All patients underwent linear accelerator (LINAC) radiotherapy. RESULTS: In MRI, all tumors and the surrounding edema were visible as hyperintense lesions in the T2-weighted images. 17/18 tumors showed contrast enhancement. In FDG-PET, 16 tumors showed hypermetabolism compared to normal white matter, whereas only 8/18 tumors showed hypermetabolism compared to normal gray matter. White matter edema was associated with decreased FDG uptake in all patients. The area of increased FDG uptake correlated closely with contrast enhancement, only in one case the volume of increased FDG uptake was larger than the area of contrast enhancement. Mean tumor volumes obtained by MRI T1 + Gd, T2, and PET were 30, 106, and 10 ml, respectively. Survival was comparable to data in the literature with a 1-year survival of 39% and a median survival of 310 days. CONCLUSION: Only in a minority of patients did FDG-PET provide additional information for radiation treatment planning. This is mainly caused by the high intensity of FDG uptake in normal brain tissue. PET may be of greater value in the definition of regions that should obtain a radiation dose boost.

Adult↗