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Biomedical subjects

Wolfgang A Weber

Publications and source records attributed to Wolfgang A Weber.

At least 19 recordsLinked to original sources
PubMed2007

Monitoring cancer treatment with PET/CT: does it make a difference?

PET with the glucose analog 18F-FDG is increasingly being used to monitor the effectiveness of therapy in patients with malignant lymphomas and a variety of solid tumors. The use of integrated PET/CT instead of stand-alone PET for treatment monitoring poses some methodologic challenges for the quantitative analysis of PET scans but also provides the opportunity to integrate morphologic information and functional information. This integration may allow the definition of new parameters for assessment of the tumor response and will also facilitate the use of PET in research studies as well as in clinical practice. This review addresses how CT-based attenuation correction may affect the quantitative analysis of 18F-FDG PET scans and summarizes the results of recent studies with PET/CT for treatment monitoring for lung cancer and gastrointestinal stromal tumors. The review concludes with an outlook on how PET/CT could make a difference in drug development and clinical management for patients.

Fluorodeoxyglucose F18↗
PubMed2006

Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction.

PURPOSE: A previous study suggested that measurement of therapy-induced changes in tumor glucose metabolism by positron emission tomography (PET) with the glucose analog [18F]fluorodeoxyglucose (FDG) allows to select patients most likely to benefit from preoperative chemotherapy in adenocarcinomas of the esophagogastric junction (AEG). The aim of this study was to prospectively validate these findings by using an a priori definition of metabolic response. PATIENTS AND METHODS: Sixty-five patients with locally advanced AEGs were included. Tumor glucose utilization was quantitatively assessed by FDG-PET before chemotherapy and 14 days after initiation of therapy. Patients were classified as metabolic responders when the metabolic activity of the primary tumor had decreased by more than 35% at the time of the second PET. RESULTS: Metabolic responders showed a high histopathologic response rate (44%) with a 3-year survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders with a histopathologic response rate of 5% (P = .001) and a 3-year survival rate of 35% (P = .01). A multivariate analysis (covariates: ypT-, ypN-category, histopathologic response) demonstrated that metabolic response was the only factor predicting recurrence (P = .018) in the subgroup of completely resected (R0) patients. CONCLUSION: This study prospectively demonstrates that changes in tumor metabolic activity during chemotherapy predict response, prognosis, and recurrence. These data provide the basis for clinical trials in which preoperative treatment is changed for patients without a metabolic response early in the course of therapy. PET-guided induction therapy may even be applicable to earlier tumor stages because surgery is only minimally delayed in nonresponding patients.

Adenocarcinoma↗
PubMed2006

Positron emission tomography as an imaging biomarker.

Positron emission tomography (PET) allows noninvasive, quantitative studies of various biologic processes in the tumor tissue. By using PET, investigators can study the pharmacokinetics of anticancer drugs, identify various therapeutic targets and monitor the inhibition of these targets during therapy. Furthermore, PET provides various markers to assess tumor response early in the course of therapy. A significant number of studies have now shown that changes in tumor glucose utilization during the first weeks of chemotherapy are significantly correlated with patient outcome. These data suggest that PET may be used as a sensitive test to assess the activity of new cytotoxic agents in phase II studies. Furthermore, early identification of nonresponding tumors provides the opportunity to adjust treatment regimens according to the individual chemosensitivity of the tumor tissue. However, further prospective and randomized validation of PET is still required before PET controlled chemotherapy can be used in clinical practice.

Antineoplastic Agents↗
PubMed2006

Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man.

PURPOSE: The integrin alpha(v)beta3 plays a key role in angiogenesis and tumor cell metastasis and is therefore an important target for new therapeutic and diagnostic strategies. We have developed [18F]Galacto-RGD, a highly alpha(v)beta3-selective tracer for positron emission tomography (PET). Here, we show, in man, that the intensity of [18F]Galacto-RGD uptake correlates with alpha(v)beta3 expression. EXPERIMENTAL DESIGN: Nineteen patients with solid tumors (musculoskeletal system, n = 10; melanoma, n = 4; head and neck cancer, n = 2; glioblastoma, n = 2; and breast cancer, n = 1) were examined with PET using [18F]Galacto-RGD before surgical removal of the tumor lesions. Snap-frozen specimens (n = 26) were collected from representative areas with low and intense standardized uptake values (SUV) of [18F]Galacto-RGD. Immunohistochemistry was done using the alpha(v)beta3-specific antibody LM609. Intensity of staining (graded on a four-point scale) and the microvessel density of alpha(v)beta3-positive vessels were determined and correlated with SUV and tumor/blood ratios (T/B). RESULTS: Two tumors showed no tracer uptake (mean SUV, 0.5 +/- 0.1). All other tumors showed tracer accumulation with SUVs ranging from 1.2 to 10.0 (mean, 3.8 +/- 2.3; T/B, 3.4 +/- 2.2; tumor/muscle ratio, 7.7 +/- 5.4). The correlation of SUV and T/B with the intensity of immunohistochemical staining (Spearman's r = 0.92; P < 0.0001) as well as with the microvessel density (Spearman's r = 0.84; P < 0.0001) were significant. Immunohistochemistry confirmed lack of alpha(v)beta3 expression in normal tissue (benign lymph nodes, muscle) and in the two tumors without tracer uptake. CONCLUSIONS: Molecular imaging of alpha(v)beta3 expression with [18F]Galacto-RGD in humans correlates with alpha(v)beta3 expression as determined by immunohistochemistry. PET with [18F]Galacto-RGD might therefore be used as a new marker of angiogenesis and for individualized planning of therapeutic strategies with alpha(v)beta3-targeted drugs.

Adult↗
PubMed2006

11C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy.

PURPOSE: To evaluate the role of 11C-methionine positron emission tomography (MET-PET) in target volume delineation for meningiomas and to determine the interobserver variability. METHODS AND MATERIALS: Two independent observers performed treatment planning in 10 patients according to a prospective written protocol. In the first step, they used coregistered computed tomography (CT) and magnetic resonance imaging (MRI). In the second step, MET-PET was added to CT/MRI (image fusion based on mutual information). RESULTS: The correlation between gross tumor volume (GTVs) delineated by the two observers based on CT/MRI was r=0.855 (Spearman's correlation coefficient, p=0.002) and r=0.988 (p=0.000) when MET-PET/CT/MRI were used. The number of patients with agreement in more then 80% of the outlined volume increased with the availability of MET-PET from 1 in 10 to 5 in 10. The median volume of intersection between the regions delineated by two observers increased significantly from 69% (from the composite volume) to 79%, by the addition of MET-PET (p=0.005). The information of MET-PET was useful to delineate GTV in the area of cavernous sinus, orbit, and base of the skull. CONCLUSIONS: The hypothesis-generating findings of potential normal tissue sparing and reduced interobserver variability provide arguments for invasive studies of the correlation between MET-PET images and histologic tumor extension and for prospective trials of target volume delineation with CT/MRI/MET-PET image fusion.

Aged↗
PubMed2006

Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction.

PURPOSE: To test whether the clinically available growth factor erythropoietin (EPO) influences radiation-induced normal-tissue damage in a model of kidney dysfunction. METHODS: Animal experiments were conducted to test the role of EPO administration in a C3H mouse model of unilateral kidney irradiation with 6, 8, and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks thereafter by means of (99m)Tc-dimercaptosuccinat scans (static scintigraphy). RESULTS: Concomitant EPO administration significantly increased the degree of radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per injection tended to cause more damage than the lower dose of 500 IU/kg. CONCLUSION: Administration of growth factors concomitant to radiotherapy might modify the development of kidney dysfunction. Although insulin-like growth factor-1 has previously been shown to protect the kidney, such an effect could not be demonstrated for EPO. The latter agent even increased the development of nephropathy.

Animals↗
PubMed2006

Monitoring chemotherapy and radiotherapy of solid tumors.

PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in numerous studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual or recurrent viable tumor and therapy-induced fibrosis or scar tissue has been documented for various solid tumors. Furthermore, there are now several reports suggesting that quantitative assessment of therapy-induced changes in tumor FDG uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. In nonresponding patients, treatment may be adjusted according to the individual chemo- and radiosensitivity of the tumor tissue. Since the number of alternative treatments for solid tumors (e.g., second-line chemotherapy agents, protein kinase, or angiogenesis inhibitors) is continuously increasing, early prediction of tumor response to chemotherapy and radiotherapy by FDG-PET has enormous potential to "personalize" treatment and to reduce the side-effects and costs of ineffective therapy.

Esophageal Neoplasms↗
PubMed2006

Molecular imaging in the development of cancer therapeutics.

Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer. New therapeutic targets have been identified and targeted therapeutic agents have been developed, but our ability to evaluate potential drugs has not kept pace. Molecular imaging technologies that monitor biological processes and/or measure levels of targeted macromolecules can contribute significantly to preclinical and clinical drug evaluation. This article describes the drug discovery process, economic problems facing drug discovery and development, and successes and failures in this realm. We briefly describe the available molecular imaging tools, with emphasis on positron emission tomography. We discuss biological processes that are altered in tumors and can be measured by molecular imaging; examples include gene expression, signal transduction, tumor cell metabolism, proliferation, apoptosis, hypoxia, and angiogenesis. We conclude with a proposal to integrate molecular imaging into the drug development process.

Drug Approval↗
PubMed2006

Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography.

STUDY OBJECTIVES: 18F-fluorodeoxyglucose (FDG) is the most widely used positron emission tomography (PET) imaging probe used for the diagnosis, staging, restaging, and monitoring therapy response of cancer. However, its specificity is less than ideal. A new molecular imaging probe (18F-deoxyfluorothymidine [FLT]) has been developed that might afford more specific tumor imaging. The aims of this study were as follows: (1) to compare the use of FDG-PET and FLT-PET for tumor staging, (2) to compare the degree of FDG and FLT uptake in lung lesions, and (3) to determine the correlation between PET uptake intensity and tumor cell proliferation. DESIGN: FDG-PET and FLT-PET scans were performed in 11 patients with solitary pulmonary nodules and another 11 patients with known non-small cell lung cancer (NSCLC). Tracer uptake was assessed quantitatively by standardized uptake values (SUVs). Histologic evaluation of tissue samples obtained from biopsy specimens or surgical resections served as the "gold standard." Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Pathology verification was available from 99 tissue samples in the 22 patients (29 pulmonary lesions, 66 lymph node stations, and 4 extrapulmonary lesions). Thirty-three samples (33.3%) were positive for tumor tissue (22 pulmonary, 9 lymph node stations, and 2 extrapulmonary). FDG-PET findings were false-positive in three pulmonary lesions, while FLT-PET findings were false-positive in one lesion. There were two false-negative findings by FDG-PET and six false-negative findings by FLT-PET. FDG uptake of the malignant lesions was significantly higher than FLT (maximum SUV, 3.1 +/- 2.6 vs 1.6 +/- 1.2 [mean +/- SD]; p < 0.05). A significant correlation was observed between FLT uptake of pulmonary lesions and Ki-67 labeling index (r = 0.60, p = 0.02) but not for FDG uptake (r = 0.27, p = not significant). CONCLUSIONS: Compared to FDG-PET, detection of primary and metastatic NSCLC by FLT-PET is limited by the relatively low FLT uptake of the tumor tissue. Thus, FLT-PET is unlikely to provide more accurate staging information or better characterization of pulmonary nodules than FDG-PET. Nevertheless, the correlation between FLT uptake and cellular proliferation suggests that future studies should evaluate the use of FLT-PET for monitoring treatment with cytostatic anticancer drugs.

Aged↗
PubMed2006

PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression.

UNLABELLED: (18)F-Galacto-RGD is a new tracer for PET imaging of alpha v beta3, a receptor involved in a variety of pathologic processes including angiogenesis and metastasis. Our aim was to study the dosimetry of (18)F-galacto-RGD in humans. METHODS: Eighteen patients with various tumors (musculoskeletal tumors [n = 10], melanoma [n = 5], breast cancer [n = 2], or head and neck cancer [n = 1]) were examined. After injection of 133-200 MBq of (18)F-galacto-RGD, 3 consecutive emission scans from the thorax to the pelvis were acquired at 6.7 +/- 2.9, 35.6 +/- 7.6, and 70.4 +/- 12.2 min after injection. Blood samples (n = 4) for metabolite analysis were taken 10, 30, and 120 min after injection. The OLINDA 1.0 program was used to estimate the absorbed radiation dose. RESULTS: Reversed-phase high-performance liquid chromatography of serum revealed that more than 95% of tracer was intact up to 120 min after injection. (18)F-Galacto-RGD showed rapid clearance from the blood pool and primarily renal excretion. Background activity in lung and muscle tissue was low (percentage injected dose per liter at 71 min after injection, 0.56 +/- 0.15 and 0.69 +/- 0.25, respectively). The calculated effective dose was 18.7 +/- 2.4 microSv/MBq, and the highest absorbed radiation dose was in the bladder wall (0.22 +/- 0.03 mGy/MBq). CONCLUSION: (18)F-Galacto-RGD demonstrates high metabolic stability, a favorable biodistribution, and a low radiation dose. Consequently, this tracer can safely be used for noninvasive imaging of molecular processes involving the alpha v beta3 integrin and for the planning and monitoring of therapeutic approaches targeting alpha v beta3.

Adult↗
PubMed2006

Impact of animal handling on the results of 18F-FDG PET studies in mice.

UNLABELLED: Small-animal PET scanning with (18)F-FDG is increasingly used in murine models of human diseases. However, the impact of dietary conditions, mode of anesthesia, and ambient temperature on the biodistribution of (18)F-FDG in mice has not been systematically studied so far. The aim of this study was to determine how these factors affect assessment of tumor glucose use by (18)F-FDG PET and to develop an imaging protocol that optimizes visualization of tumor xenografts. METHODS: Groups of severe combined immunodeficient (SCID) mice were first imaged by microPET with free access to food, at room temperature (20 degrees C), and no anesthesia during the uptake period (reference condition). Subsequently, the impact of (a) fasting for 8-12 h, (b) warming the animals with a heating pad (30 degrees C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the (18)F-FDG biodistribution was evaluated. Subcutaneously implanted human A431 epidermoid carcinoma and U251 glioblastoma cells served as tumor models. RESULTS: Depending on the study conditions, (18)F-FDG uptake by normal tissues varied 3-fold for skeletal muscle, 13-fold for brown adipose tissue, and 15-fold for myocardium. Warming and fasting significantly reduced the intense (18)F-FDG uptake by brown adipose tissue observed under the reference condition and markedly improved visualization of tumor xenografts. Although tumor (18)F-FDG uptake was not above background activity under the reference condition, tumors demonstrated marked focal (18)F-FDG uptake in warmed and fasted animals. Quantitatively, tumor (18)F-FDG uptake increased 4-fold and tumor-to-organ ratios were increased up to 17-fold. Ketamine/xylazine anesthesia caused marked hyperglycemia and was not further evaluated. Isoflurane anesthesia only mildly increased blood glucose levels and had no significant effect on tumor (18)F-FDG uptake. Isoflurane markedly reduced (18)F-FDG uptake by brown adipose tissue and skeletal muscle but increased the activity concentration in liver, myocardium, and kidney. CONCLUSION: Animal handling has a dramatic effect on (18)F-FDG biodistribution and significantly influences the results of microPET studies in tumor-bearing mice. To improve tumor visualization mice should be fasted and warmed before (18)F-FDG injection and during the uptake period. Isoflurane appears well suited for anesthesia of tumor-bearing mice, whereas ketamine/xylazine should be used with caution, as it may induce marked hyperglycemia.

Animal Husbandry↗
PubMed2005

Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy.

PURPOSE: To develop a valid treatment strategy for recurrent high-grade gliomas using stereotactic hypofractionated reirradiation based on biologic imaging and temozolomide. PATIENTS AND METHODS: The trial included a total of 44 patients with recurrent high-grade gliomas (1 patient with anaplastic oligodendroglioma, 8 with anaplastic astrocytoma, 33 with glioblastoma multiforme, and 2 with gliosarcoma) after previous surgery and postoperative conventional radiotherapy +/- chemotherapy. For fractionated stereotactic radiotherapy (SFRT) treatment planning, the gross tumor volume was defined by (11)C-methionine positron emission tomography (MET-PET) or (123)I-alpha-methyl-tyrosine (IMT) single-photon computed emission tomography (SPECT)/computed tomography (CT)/magnetic resonance imaging (MRI) fusion in 82% of the patients and by CT/T1+gadolinium-MRI image fusion in 18% of the patients. Six fractions of 5 Gy were administered in 6 days. In 29 of 44 patients (66%), chemotherapy with temozolomide (200 mg/m(2) body surface/day) was given in one to two cycles before and four to five cycles after SFRT. The patients were evaluated in follow-up by clinical investigators and MRI or CT every 3 months after SFRT until death. In cases suspicious for radiation necrosis, a MET-PET or IMT-SPECT investigation was performed. RESULTS: The median survival time in the whole group was 8 months. Treatment planning based on PET(SPECT)/CT/MRI imaging was associated with improved survival in comparison to treatment planning using CT/MRI alone: median survival time 9 months vs. 5 months (p = 0.03, log-rank). Median survival time were 11 months for patients who received SFRT based on biologic imaging plus temozolomide and significantly lower, 6 months for patients treated with SFRT without biologic imaging, without temozolomide or without both (p = 0.008, log rank). The most important prognostic factor in univariate analysis was a long interval between initial diagnosis and recurrence (p = 0.0002, log-rank). In the multivariate model, time interval to retreatment (p = 0.006) and temozolomide (p = 0.04) remained statistically significant. No acute neurologic toxicity Grade 3 or higher and no Grade 4 hematologic toxicity was observed. CONCLUSION: This is the first study of biologic imaging optimized SFRT plus temozolomide in recurrent high-grade gliomas. It demonstrates the feasibility and safety of this approach. The most striking result of the trial is the statistically significant longer survival time in the univariate analysis for patients reirradiated using MET-PET or IMT-SPECT/CT/MRI image fusion in the treatment planning, in comparison to patients treated based on MRI/CT alone. Multivariate analysis confirmed a significant survival benefit from multimodal treatment (i.e., addition of temozolomide), despite the limited number of patients. Whether treatment planning with SPECT/PET independently influences survival has to be studied in a larger series of patients.

Adult↗
PubMed2005

Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer.

PURPOSE: The aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer. PATIENTS AND METHODS: Thirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference. RESULTS: A significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival. CONCLUSION: Sequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.

Adult↗
PubMed2005

L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy.

PURPOSE: Using magnetic resonance imaging (MRI), residual tumor cannot be differentiated from nonspecific postoperative changes in operated patients with brain gliomas. The higher specificity and sensitivity of L-(methyl-11C)-labeled methionine positron emissions tomography (MET-PET) in gliomas has been demonstrated in previous studies and is the rationale for the integration of this investigation in gross tumor volume delineation. The goal of this trial was to quantify the affect of MET-PET vs. with MRI in gross tumor volume definition for radiotherapy planning of high-grade gliomas. METHODS AND MATERIALS: The trial included 39 patients with resected malignant gliomas. MRI and MET-PET data were coregistered based on mutual information. The residual tumor volume on MET-PET and the volume of tissue abnormalities on T1-weighted MRI (gadolinium [Gd] enhancement) and T2-weighted MRI (hyperintensity areas) were compared using MET-PET/MRI fusion images. RESULTS: The MET-PET vs. Gd-enhanced T1-weighted MRI analysis was performed on 39 patients. In 5 patients (13%), MET uptake corresponded exactly with Gd enhancement, and in 29 (74%) of 39 patients, the region of MET uptake was larger than that of the Gd enhancement. In 27 (69%) of the 39 patients, the Gd enhancement area extended beyond the MET enhancement. MET uptake was detected up to 45 mm beyond the Gd enhancement. MET-PET vs. T2-weighted MRI was investigated in 18 patients. MET uptake did not correspond exactly with the hyperintensity areas on T2-weighted MRI in any patient. In 9 (50%) of 18 patients, MET uptake extended beyond the hyperintensity area on the T2-weighted MRI, and in 18 (100%), at least some hyperintensity on the T2-weighted MRI was located outside the MET enhancement area. MET uptake was detected up to 40 mm beyond the hyperintensity area on T2-weighted MRI. CONCLUSION: In operated patients with brain gliomas, the size and location of residual MET uptake differs considerably from abnormalities found on postoperative MRI. Because postoperative changes cannot be differentiated from residual tumor by MRI, MET-PET, with a greater specificity for tumor tissue, can help to outline the gross tumor volume with greater accuracy.

Adult↗
PubMed2005

Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD.

BACKGROUND: The integrin alphavbeta3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of alphavbeta3 expression. We developed [(18)F]Galacto-RGD, a (18)F-labeled glycosylated alphavbeta3 antagonist, allowing monitoring of alphavbeta3 expression with positron emission tomography (PET). METHODS AND FINDINGS: Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [(18)F]Galacto-RGD in the tumor correlates with alphavbeta3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize alphavbeta3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [(18)F]Galacto-RGD with PET enables noninvasive quantitative assessment of the alphavbeta3 expression pattern on tumor and endothelial cells in patients with malignant tumors. CONCLUSIONS: Molecular imaging with [(18)F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the alphavbeta3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.

Animals↗
PubMed2005

Positron emission tomography for radiation treatment planning.

PURPOSE: To evaluate the impact of positron emission tomography (PET) on target volume delineation for radiation treatment planning. MATERIAL AND METHODS: The data of the literature concerning the use of PET in target volume delineation are summarized. The following points are discussed for each tumor entity: biological background for the PET investigation, sensitivity and specificity of PET (with different tracers) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) and impact of PET on target volume definition. New PET tracers, which could visualize biological pathways, such as hypoxia, proliferation, angiogenesis, apoptosis and gene expression patterns, will also be discussed. RESULTS: The results of clinical studies on the integration of PET in target volume definition for lung, head-and-neck, genitourinary and brain tumors were analyzed. Fluorodeoxyglucose-(FDG-)PET has a significant impact on GTV (gross tumor volume) and PTV (planning target volume) delineation in lung cancer and can detect lymph node involvement and differentiate malignant tissue from atelectasis. In head-and-neck cancer, the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET could be superior to CT and MRI in the detection of lymph node metastases and unknown primary cancer and in the differentiation of viable tumor tissue after treatment. Therefore, it might play an important role in GTV definition and sparing of normal tissue. Choline PET and acetate PET are promising tracers in the diagnosis of prostate cancer, but their validity in local tumor demarcation, lymph node diagnosis and detection of recurrence has to be defined in future clinical trials. FDG-PET seems to be particularly valuable in lymph node status definition in cervical cancer. In high-grade gliomas and meningiomas, methionine PET helps to define the GTV and differentiate tumor from normal tissue. For other entities like gastrointestinal cancer, lymphomas, sarcomas, etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can individually be targeted using intensity modulated radiotherapy (IMRT). In addition, a biological dose distribution can be generated, the socalled dose painting. However, systematic experimental and clinical trials are necessary to validate this hypothesis. CONCLUSION: Regarding treatment planning in radiotherapy, PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, subsequent experimental, clinical and cost-benefit analyses are required.

Brain Neoplasms↗
PubMed2005

Monitoring response to treatment in patients utilizing PET.

Establishing new surrogate end points for monitoring response to treatment is needed for current therapy modalities and for new therapeutic strategies including molecular targeted cancer therapies. PET as a functional imaging technology provides rapid, reproducible, noninvasive in vivo assessment and quantification of several biologic processes targeted by these therapies. PET is useful in a variety of clinical relevant applications, including distinguishing between radiation necrosis and tumor recurrence, determining the resectability of recurrent tumor, and evaluating response to therapy. FDG-PET has demonstrated efficacy for monitoring therapeutic response in a wide range of cancers, including breast, esophageal, lung, head and neck, and lymphoma. FDG-PET can assess tumor glucose use with high reproducibility. Following therapy, the decrease of glucose use correlates with the reduction of viable tumor cells. FDG-PET allows the prediction of therapy response early in the course of therapy and determining the viability of residual masses after completion of treatment. The molecular basis for the success of FDG-PET is the rapid reduction of tumor glucose metabolism in effective therapies. Of even higher clinical relevance is the accurate identification of nonresponders in patients without a significant change in tumor glucose metabolism after initiation of therapy. PET imaging can easily visualize these changes in metabolic activity and indicate, sometimes within hours of the first treatment, whether or not a patient will respond to a particular therapy. In contrast to CT, MR imaging, or ultrasound, PET imaging allows identification of responding and nonresponding tumors early in the course of therapy. With this information, physicians can rapidly modify ineffective therapies for individual patients and thereby potentially improve patient outcomes and reduce cost. One of the major limitations for the routine application of FDG-PET imaging for therapy monitoring is that no generally accepted cutoff values have been established to differentiate optimally between responders and nonresponders. The patient series are still relatively small and frequently consist of different tumor types and different therapy regimens. Prospective studies including a sufficient number of patients are needed to define cutoff values to differentiate between responder and nonresponder for different tumors and different treatment regimes. In the future, PET imaging can also serve in the evaluation of new therapeutic agents, new experimental treatments, and specifically in monitoring clinical phase II studies.

Fluorodeoxyglucose F18↗