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Markus Schwaiger

Publications and source records attributed to Markus Schwaiger.

At least 19 recordsLinked to original sources
PubMed2007

Non-invasive visualisation of the development of peritoneal carcinomatosis and tumour regression after 213Bi-radioimmunotherapy using bioluminescence imaging.

PURPOSE: Non-invasive imaging of tumour development remains a challenge, especially for tumours in the intraperitoneal cavity. Therefore, the aim of this study was the visualisation of both the development of peritoneal carcinomatosis and tumour regression after radioimmunotherapy with tumour-specific 213Bi-Immunoconjugates, via in vivo bioluminescence imaging of firefly luciferase-transfected cells. METHODS: Human diffuse-type gastric cancer cells expressing mutant d9-E-cadherin were stably transfected with firefly luciferase (HSC45-M2-luc). For bioluminescence imaging, nude mice were inoculated intraperitoneally with 1x10(7) HSC45-M2-luc cells. On days 4 and 8 after tumour cell inoculation, imaging was performed following D-luciferin injection using a cooled CCD camera with an image intensifier unit. For therapy, mice were injected with 2.7 MBq 213Bi-d9MAb targeting d9-E-cadherin on day 8 after tumour cell inoculation. Bioluminescence images were taken every 4 days to monitor tumour development. RESULTS: After i.p. inoculation of HSC45-M2-luc cells into nude mice, development as well as localisation of peritoneal carcinomatosis could be visualised using bioluminescence imaging. Following 213Bi-d9MAb therapy on day 8 after intraperitoneal inoculation of HSC45-M2-luc cells, small tumour nodules were totally eliminated and larger nodules showed a clear reduction in size on day 12 after tumour cell inoculation. Subsequently a recurrence of tumour mass was observed, starting from the remaining tumour spots. By measuring the mean grey level intensity, tumour development over time could be demonstrated. CONCLUSION: Non-invasive bioluminescence imaging permits visualisation of the development of peritoneal carcinomatosis, localisation of tumour in the intraperitoneal cavity and evaluation of therapeutic success after 213Bi-d9MAb treatment.

Animals↗
PubMed2006

PET imaging with [18F]3'-deoxy-3'-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer.

PURPOSE: Positron emission tomography (PET) using 18F-labelled 3'-deoxy-3'-fluorothymidine (FLT) was assessed for therapy monitoring in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. METHODS: Ten patients with locally advanced rectal cancer were included and underwent long-course preoperative chemoradiotherapy (total dose 45 Gy, 1.8 Gy/day, concomitant 250 mg/m2 5-fluorouracil) followed by surgery. FLT-PET was performed prior to chemoradiotherapy, 2 weeks after initiation of chemoradiotherapy and preoperatively (3-4 weeks post chemoradiotherapy). FLT uptake was correlated with histopathological tumour regression and changes in T stage. RESULTS: Mean tumour FLT uptake was 4.2+/-1.0 SUV before therapy and decreased significantly to 2.9+/-0.6 SUV 14 days after initiation of chemoradiotherapy (-28.6%+/-10.7%, p=0.005). The preoperative scan showed a further decrease to 1.9+/-0.4 SUV (-54.7%+/-7.6%, p=0.005). However, the degree of change in FLT uptake 2 weeks after initiation and after completion of neoadjuvant therapy did not correlate with histopathological tumour regression. CONCLUSION: FLT-PET did not seem to be a promising method for assessment of tumour response in the studied chemoradiotherapy regimen in patients with rectal cancer.

Adult↗
PubMed2006

Diagnostic value of contrast-enhanced magnetic resonance imaging and single-photon emission computed tomography for detection of myocardial necrosis early after acute myocardial infarction.

OBJECTIVES: This study sought to evaluate the diagnostic value of contrast-enhanced magnetic resonance imaging (CMR) and single-photon emission computed tomography (SPECT) for detection of myocardial necrosis after acute myocardial infarction (AMI). BACKGROUND: Single-photon emission computed tomography is widely accepted in the clinical setting for detection and estimation of myocardial infarction. Contrast-enhanced magnetic resonance imaging offers technical advantages and is therefore a promising new method for identification of infarcted tissue. METHODS: Seventy-eight patients with AMI were examined by CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced magnetic resonance imaging and SPECT images were scored for presence and location of infarction using a 17-segment model. Results were compared with the peak troponin T level, electrocardiographic, and angiographic findings. RESULTS: Acute myocardial infarction was detected significantly more often by CMR than SPECT (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to SPECT in detecting small infarction as assessed by the peak troponin T level <3.0 ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs. 84%; p = 0.03). Non-Q-wave infarctions were more likely to be detected by CMR (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for detection of AMI irrespective of the infarct-related artery, SPECT was less sensitive, particularly within the left circumflex artery territory. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging is superior to SPECT in detecting myocardial necrosis after reperfused AMI because CMR detects small infarcts that were missed by SPECT independent of the infarct location. Thus, CMR is attractive for accurate detection and assessment of the myocardial infarct region in patients early after AMI.

Aged↗
PubMed2006

Performance evaluation of the Philips MOSAIC small animal PET scanner.

PURPOSE: In this study an evaluation of the performance of the Philips MOSAIC small animal PET scanner is presented, with special emphasis on the ability of the system to provide quantitatively accurate PET images. METHODS: The performance evaluation was structured according to NEMA-like procedures. RESULTS: The transaxial spatial resolution of the system (radial component) ranged between 2.7 mm FWHM at the centre and 3.2 mm FWHM at a radial offset of 45 mm from the centre. The axial spatial resolution of the system ranged between 3.4 mm FWHM at the centre and 5.8 mm FWHM at a radial offset of 45 mm from the centre. The scatter fraction was determined for a mouse- as well as for a rat-sized phantom, and the values obtained were 9.6% and 16.8%, respectively. For the mouse phantom, the maximum count rate measured was 560 kcps at 93 MBq; the maximum NEC rate equalled 308 kcps at 1.7 MBq/ml. For the rat phantom, these values were 400 kcps at 100 MBq and 129 kcps at 0.24 MBq/ml, respectively. The sensitivity of the system was derived to be 0.65%. An energy window between 410 and 665 keV was used in all experiments. CONCLUSION: The MOSAIC system exhibits moderate spatial resolution and sensitivity values, but good NEC performance. In combination with its relatively large field of view, the system allows for high-throughput whole-body imaging of mice and rats. The accurate measurement of relative changes in radiotracer distributions is feasible.

Animals↗
PubMed2006

Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.

OBJECTIVES: We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention. BACKGROUND: Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques. METHODS: In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed. RESULTS: Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis. CONCLUSIONS: Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.

Animals↗
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 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

Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer's disease: a double-blind cross-over trial.

RATIONALE: Cholinergic enhancement is among the best established treatments of Alzheimer's disease (AD). The cognitive effects of treatment are thought to be mediated by improvement of neuronal transmission. Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) by measuring cortical metabolic response to activation assesses integrity of neuronal transmission in vivo. OBJECTIVE: To determine the effects of treatment with donepezil, a centrally selective acetylcholinesterase inhibitor, on cortical metabolism in AD using 18FDG-PET. METHODS: We enrolled 23 patients, 18 of which completed the study, with mild to moderate probable AD (mini-mental status exam scores of 15-28, inclusive) in a double-blind cross over trial of 8 weeks donepezil compared to 8 weeks placebo with repeated double 18FDG-PET examinations during passive audio-visual stimulation. Effects of treatment on cortical metabolic response to stimulation were determined with a linear model on a voxel level using Statistical Parametric Mapping (SPM 99, Wellcome Department of Imaging Neuroscience, London). RESULTS: Effects of treatment on cognitive measures were not different between donepezil and placebo. During passive audio-visual stimulation, patients showed activation in posterior visual and auditory areas and decreased activation in frontal cortex and basal ganglia. Resting state metabolism was increased with donepezil in left prefrontal cortex and decreased in right hippocampus. Cortical response to activation was increased in right hippocampus with donepezil compared to placebo. CONCLUSION: Donepezil treatment shows a spatially limited functional effect on right hippocampus and left prefrontal cortical metabolism, independently of clinical response to treatment.

Aged↗
PubMed2006

[(111)In]DOTATOC as a dosimetric substitute for kidney dosimetry during [(90)Y]DOTATOC therapy: results and evaluation of a combined gamma camera/probe approach.

PURPOSE: During [(90)Y]DOTATOC therapy, for determination of kidney doses a conventional approach using co-injected [(111)In]DOTATOC was evaluated for validity, reliability and reproducibility as well as for the influence of methodological variations and bremsstrahlung. Biologically effective doses were estimated by calculating the relative effectiveness (RE) of kidney doses. METHODS: Fractionated [(90)Y]DOTATOC therapy (n=20 patients, 3.1+/-0.7 GBq/therapy cycle, 45 therapy cycles) included co-injection of 157+/-37 MBq [(111)In]DOTATOC and a nephroprotective infusion regimen. From serial gamma camera/probe measurements, individual region of interest (ROI) sets were established and kidney doses were determined according to MIRDOSE3 (corrected for individual kidney mass) by use of three methodological variants: (1) correction for interfering organs (liver/spleen) and background activity, (2) correction for interfering organs alone and (3) no corrections. A phantom study was performed with (111) In alone and with (111)In +(90)Y to estimate the influence of (90)Y bremsstrahlung. RESULTS: Mean kidney dose (method 1, n=20 patients, 20 therapy cycles) was 1.51+/-0.60 Gy/GBq [(90)Y]DOTATOC (1.41+/-0.48 Gy/GBq for n=20 patients, 45 therapy cycles). With partial correction (method 2) or no correction (method 3) for interfering activity, kidney doses increased significantly, to 2.71+/-1.26 Gy/GBq and 3.15+/-1.22 Gy/GBq, respectively. The span of REs ranged from 1.02 to 1.24. Inter-observer variability was as high as +/-32% (+/-2SD). (90)Y bremsstrahlung accounted for a 4-11% underestimation of obtained target activity. CONCLUSION: The obtained kidney doses are highly influenced by methodological variations. Full correction for interfering activity clearly underestimates kidney doses. By comparison, (90)Y bremsstrahlung and variability in the relative effectiveness of kidney doses cause minor bias. Inter-observer variability must be considered when interpreting kidney doses.

Female↗
PubMed2006

Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells.

PURPOSE: Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics. METHODS: For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L: -serine. RESULTS: All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V (max)) and affinity (K (m)) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells. CONCLUSION: In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.

Cells, Cultured↗
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

N-terminal pro-brain natriuretic peptide on admission in patients with acute myocardial infarction and correlation with scintigraphic infarct size, efficacy of reperfusion, and prognosis.

We investigated whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) that was measured on admission in patients with acute myocardial infarction (AMI) predicts the efficacy of reperfusion or whether NT-pro-BNP provides prognostic information independent of infarct size as estimated by single-photon emission computed tomographic scintigraphy. The study included 174 patients with ST-segment elevation AMI who were admitted within 24 hours of pain onset. NT-pro-BNP level was measured on admission. Paired scintigraphic studies (before and 7 to 14 days after reperfusion) were performed to assess infarct size and define myocardial salvage. One-year clinical follow-up was assessed. Patients were categorized into the high NT-pro-BNP group (57 patients in the upper tertile of NT-pro-BNP) and low NT-pro-BNP group (117 patients in the middle and lower tertiles of NT-pro-BNP). Initial median perfusion defect was 35.0% (interquartile rage 20.0 to 53.0%) of the left ventricle in the high NT-pro-BNP group versus 19.0% (interquartile range 10.0 to 32.2) of the left ventricle in the low NT-pro-BNP group (p <0.001). Median salvage index was 0.36 (interquartile range 0.16 to 0.86) in the high NT-pro-BNP group versus 0.53 (interquartile range 0.31 to 0.75) in the low NT-pro-BNP group (p = 0.22). After adjustment in Cox's proportional hazards model, NT-pro-BNP remained an independent correlate of 1-year mortality (adjusted hazard ratio 2.31, 95% confidence interval 1.09 to 4.89, p = 0.03, high vs low NT-pro-BNP group). In conclusion, NT-pro-BNP measured on admission in patients with AMI correlates with scintigraphic area at risk and predicts prognosis but does not predict the efficacy of mechanical reperfusion by stenting or angioplasty.

Aged↗
PubMed2006

Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial.

CONTEXT: Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow-derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells. OBJECTIVE: To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005. INTERVENTIONS: Patients were randomly assigned to receive subcutaneously either a daily dose of 10 microg/kg of G-CSF or placebo for 5 days. MAIN OUTCOME MEASURES: The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis. RESULTS: Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort. CONCLUSION: Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00126100.

Aged↗
PubMed2006

High-precision radiation therapy with integrated biological imaging and tumor monitoring: evolution of the Munich concept and future research options.

PURPOSE: To describe an emerging concept of high-precision radiotherapy, a modality characterized by adaptation to patient and organ movements, which might occur between fractions or even during radiation delivery. METHODS AND RESULTS: Today's unprecedented technical capabilities to visualize the target volume and create conformal dose distributions allow for avoidance of critical structures or targeted treatment intensification within a conventionally imaged, anatomically defined tumor. The success of selective dose escalation depends on (1) correct staging and target volume identification, which can be improved by biological imaging, and (2) identification of biologically relevant subvolumes, which determine tumor control. Current efforts are directed at different methods, such as positron emission tomography and magnetic resonance spectroscopy, and integrating them into treatment planning. CONCLUSION: Early clinical trials assessing the safety and efficacy of image- and biology-guided radiotherapy are ongoing. The same modalities might be used to determine the individual tumor response during treatment and to adapt therapy. Temporal changes in tumor biology, which might represent both a challenge and a chance with regard to adaptation of treatment, need to be addressed in greater detail.

Animals↗