Prediction of synchronous distant metastasis of primary pancreatic ductal adenocarcinoma using the radiomics features derived from 18F-FDG PET and MRI.

AIM: To explore the potential of the joint radiomics analysis of positron-emission tomography (PET) and magnetic resonance imaging (MRI) of primary tumours for predicting the risk of synchronous distant metastasis (SDM) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: 18F-FDG PET and MRI images of PDAC patients from January 2011 to December 2020 were collected retrospectively. Patients (n=66) who received 18F-FDG PET/CT and MRI were included in a development group. Patients (n=25) scanned with hybrid PET/MRI were incorporated in an external test group. A radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm to select PET-MRI radiomics features of primary PDAC tumours. A radiomics nomogram was developed by combining the radiomics signature and important clinical indicators using univariate and multivariate analysis to assess patients' metastasis risk. The nomogram was verified with the employment of an external test group. RESULTS: Regarding the development cohort, the radiomics nomogram was found to be better for predicting the risk of distant metastasis (area under the curve [AUC]: 0.93, sensitivity: 87%, specificity: 85%) than the clinical model (AUC: 0.70, p<0.001; sensitivity:70%, specificity: 65%) and the radiomics signature (AUC: 0.89, p>0.05; sensitivity: 65%, specificity:100%). Concerning the external test cohort, the radiomics nomogram yielded an AUC of 0.85. CONCLUSION: PET-MRI based radiomics analysis exhibited effective prediction of the risk of SDM for preoperative PDAC patients and may offer complementary information and provide hints for cancer staging.

Three-dimensional fat-saturated T1-weighted Cartesian volumetric interpolated breath-hold examination (VIBE) for the diagnosis of aortitis in patients with suspected large vessel vasculitis: a comparative study with 18F-FDG PET applying fully integrated PET/MRI.

AIM: To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/MRI. MATERIAL AND METHODS: Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results. RESULTS: On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p<0.0001). CONCLUSION: T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV.

[Combined PET-MRI of the abdomen]. / Kombinierte PET-MRT des Abdomens.

The first fully integrated combined positron emission tomography-magnetic resonance imaging (PET-MRI) scanners have been clinically available since 2010. Large prospective studies regarding indications and diagnostic accuracy of this new modality are not yet available; however, preliminary studies have shown a higher diagnostic accuracy and confidence compared to PET-computed tomography (PET-CT) in regions where MRI is known to be superior to CT, such as the liver. The benefit of MRI in accurate lesion characterization and the additional value of diffusion-weighted imaging (DWI) as a complementary functional modality by means of the apparent diffusion coefficient (ADC) is apparent in entities with low tracer uptake (e.g. due to small size) and a decreased or absent accumulation pattern on PET.

Apparent rate constant mapping using hyperpolarized [1-(13)C]pyruvate.

Hyperpolarization of [1-13C]pyruvate in solution allows real-time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate. In this work, we present comprehensive methods for the quantification and interpretation of hyperpolarized 13C metabolite signals. First, a time-domain spectral fitting method is described for the decomposition of FID signals into their metabolic constituents. For this purpose, the required chemical shift frequencies are automatically estimated using a matching pursuit algorithm. Second, a time-discretized formulation of the two-site exchange kinetic model is used to quantify metabolite signal dynamics by two characteristic rate constants in the form of (i) an apparent build-up rate (quantifying the build-up of downstream metabolites from the pyruvate substrate) and (ii) an effective decay rate (summarizing signal depletion due to repetitive excitation, T1-relaxation and backward conversion). The presented spectral and kinetic quantification were experimentally verified in vitro and in vivo using hyperpolarized [1-13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build-up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build-up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies.

Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

Sodium iodide symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus.

In this study, we determined the in vitro and in vivo efficacy of sodium iodide symporter (NIS) gene transfer and the therapeutic potential of oncolytic virotherapy combined with radioiodine therapy using a conditionally replicating oncolytic adenovirus. For this purpose, we used a replication-selective adenovirus in which the E1a gene is driven by the mouse alpha-fetoprotein (AFP) promoter and the human NIS gene is inserted in the E3 region (Ad5-E1/AFP-E3/NIS). Human hepatocellular carcinoma cells (HuH7) infected with Ad5-E1/AFP-E3/NIS concentrated radioiodine at a level that was sufficiently high for a therapeutic effect in vitro. In vivo experiments demonstrated that 3 days after intratumoral (i.t.) injection of Ad5-E1/AFP-E3/NIS HuH7 xenograft tumors accumulated approximately 25% ID g(-1) (percentage of the injected dose per gram tumor tissue) (123)I as shown by (123)I gamma camera imaging. A single i.t. injection of Ad5-E1/AFP-E3/NIS (virotherapy) resulted in a significant reduction of tumor growth and prolonged survival, as compared with injection of saline. Combination of oncolytic virotherapy with radioiodine treatment (radiovirotherapy) led to an additional reduction of tumor growth that resulted in markedly improved survival as compared with virotherapy alone. In conclusion, local in vivo NIS gene transfer using a replication-selective oncolytic adenovirus is able to induce a significant therapeutic effect, which can be enhanced by additional (131)I application.

Surgical site infections in orthognathic surgery: prolonged versus single-dose antibiotic prophylaxis.

The oral cavity is densely populated with microorganisms. As a result, intraoral surgical sites are prone to contamination by pathogens, potentially triggering surgical site infections (SSIs). Prophylactic antibiotics have proven beneficial in reducing the rate of SSIs. However, no consensus has been reached regarding the most effective regimen. The purpose of this study was to investigate two different antibiotic regimens - single-dose and prolonged antibiotic prophylaxis - regarding the rate and severity of postoperative SSIs in patients undergoing orthognathic surgery. Data were analysed retrospectively. Patients who underwent bilateral sagittal split ramus osteotomy or bimaxillary surgery in the study department in 2017 were screened for eligibility. Ninety-nine patients were included in the study and were divided into two groups. The prolonged-antibiotic prophylaxis group (PAP; n = 49) received a 5-day antibiotic prophylaxis regimen, while the single-dose antibiotic prophylaxis group (SDAP; n = 50) received single-dose antibiotic prophylaxis. The groups were assessed for the rate and severity of SSIs following orthognathic surgery. Five patients (10.2%) in the PAP group and seven (14%) in the SDAP group developed infections; no statistically significant difference in the occurrence of SSIs was found (P = 0.380). Single-dose antibiotic prophylaxis is as effective as a 5-day antibiotic prophylaxis regimen in preventing SSIs in orthognathic surgery and is a suitable antibiotic prophylaxis option when considering the risk of antibiotic resistance.

Effects of pyruvate dose on in vivo metabolism and quantification of hyperpolarized ¹³C spectra.

Real-time in vivo measurements of metabolites are performed by signal enhancement of [1-(13)C]pyruvate using dynamic nuclear polarization, rapid dissolution and intravenous injection, acquisition of free induction decay signals and subsequent quantification of spectra. The commonly injected dose of hyperpolarized pyruvate is larger than typical tracer doses, with measurement before complete dilution of the injected bolus. Pyruvate is in exchange with its downstream metabolites lactate, alanine and bicarbonate. A transient exposure to high pyruvate blood concentrations may cause the saturation of cellular uptake and metabolic conversion. The goal of this study was to examine the effects of a [1-(13)C]pyruvate bolus on metabolic conversion in vivo. Spectra were quantified by three different methods: frequency-domain fitting with LCModel, time-domain fitting with AMARES and simple linear least-squares fitting in the time domain. Since the simple linear least-squares approach showed bleeding artifacts and LCModel produced noisier time signals. AMARES performed best in the quantification of in vivo hyperpolarized pyruvate spectra. We examined pyruvate doses of 0.1-0.4 mmol/kg (body mass) in male Wistar rats by acquiring slice-selective free induction decay signals in slices dominated by heart, liver and kidney tissue. Dose effects were noted in all cases, except for alanine in the cardiac slice below the dose of 0.2 mmol/kg. Our results indicate unlimited cellular uptake of pyruvate up to this dose and limited enzymatic activity of lactate dehydrogenase. In the cardiac slice above 0.2 mmol/kg and in liver and kidney slices, reflect limited cellular uptake or enzymatic activity, or a combination of both effects. The results indicate that the dose of pyruvate must be recognized as an important determinant for metabolic tissue kinetics, and saturation effects must be taken into account for the quantitative interpretation of the observed results.

Respiratory gated [18F]FDG PET/CT for target volume delineation in stereotactic radiation treatment of liver metastases.

PURPOSE: The use of 4D-[(18)F]fluorodeoxyglucose (FDG) PET/CT in combination with respiratory gated magnet resonance imaging (MRI) in target volume definition for stereotactic radiation of liver metastases was investigated. METHODS AND MATERIALS: A total of 18 patients received respiration gated FDG-PET/CT and MRI. Data were fused using a rigid co-registration algorithm. The quality of the co-registration was rated on a scale from 1 (excellent) to 5 (poor) for co-registration of MRI with gated PET and ungated PET. Gross tumor volume (GTV) was delineated in CT (GTV (CT)), MRI (GTV(MRI)), and PET (GTV(PET)). MRI- and PET-based GTVs were defined by three observers each. Interobserver variability was calculated for all patients as well as for subgroups with and without previous treatment of liver metastases. All GTVs were compared for all patients and separately for patients with previous local therapy. In addition, a semiautomatic segmentation algorithm was applied on the PET images. RESULTS: Co-registration between MR and PET images was rated with 3.3 in average when non-gated PET was used and improved significantly (p < 0.01) to 2.1 using gated PET. The average GTV(CT) was 51.5 ml, GTV(MRI) 51.8 ml, and the average GTV(PET) 48.1 ml. Volumes delineated in MRI were 9.9% larger compared to those delineated in CT. Volumes delineated in PET were 13.8% larger than in MRI. The differences between the GTVs were more pronounced in patients with previous treatment. The GTVs defined in MRI showed an interobserver variability of 47.9% (84.1% with previous treatment and 26.2% without previous treatment). The PET-defined GTVs showed an interobserver variability of 21% regardless of previous treatment. Semiautomatic segmentation did not provide satisfying results. CONCLUSION: FDG-PET can distinguish vital tumor tissue and scar tissue, and therefore alters the GTV especially in patients with previous local treatment. In addition, it reduces the interobserver variability significantly compared to MRI. However, respiratory gated PET is necessary for good co-registration of PET and MRI.

Radiolabelled RGD peptides for imaging and therapy.

Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin α(v)ß(3). For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of α(v)ß(3) expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy.

Comparison of 3'-deoxy-3'-[¹8F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours.

PURPOSE: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery. METHODS: A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images. RESULTS: Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV(max) 1.1-6.5; mean FDG SUV(max) 7.9, range 3.3-17.8; p < 0.001). CONCLUSION: For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology.

The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of "population images" that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures. Key Points • New diagnostic technologies are yielding unprecedented amounts of diagnostic information.• Advanced IT/cloud computing will aid integration and analysis of diagnostic data.• Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.

Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion.

Obesity is associated with increased risk for developing pancreatic cancer, and it is suggested that insulin resistance provides the missing link. Here we demonstrate that under the context of genetic susceptibility, a high fat diet (HFD) predisposes mice with oncogenic K-ras activation to accelerated pancreatic intraepithelial neoplasm (PanIN) development. Tumor promotion is closely associated with increased inflammation and abrogation of TNFR1 signaling significantly blocks this process underlining a central role for TNFalpha in obesity-mediated enhancement of PanIN lesions. Interestingly, however, despite increased TNFalpha levels, mice remain insulin sensitive. We show that, while aggravating tumor promotion, a HFD exerts dramatic changes in energy metabolism through enhancement of pancreatic exocrine insufficiency, metabolic rates, and expression of genes involved in mitochondrial fatty acid (FA) beta-oxidation that collectively contribute to improved glucose tolerance in these mice. While on one hand these findings provide significant evidence that obesity is linked to tumor promotion in the pancreas, on the other it suggests alterations in inflammatory responses and bioenergetic pathways as the potential underlying cause.

Determination of blood loss in bimaxillary surgery: does the formula and the time point affect results?

The amount of blood loss determined in orthognathic surgery differs greatly among studies. This can be attributed to the inhomogeneity in study cohorts analysed, but may also be a result of the varying methodologies used for blood loss determination. However, this has yet to be explored. Thus, the aim of this study was to investigate the extent to which the formula and time point used to measure blood loss affect the blood loss volume, determined in a homogeneous cohort undergoing bimaxillary surgery. Blood loss was calculated at 24 and 48 hours postoperatively using the haemoglobin balance method and the formula of Hurle et al. The estimated total blood volume was established based on the formulae of Nadler et al. and Choi et al. Differences in blood loss volume with respect to time point and formula were analysed and compared. Fifty-four patients were included in the final analysis. Statistically significant differences in blood loss were observed: a significant increase in the blood loss volume from 24 hours to 48 hours postoperatively was detected. When comparing the formulae used, blood loss differed significantly at 24 hours after surgery; however no such difference resulted at 48 hours postoperatively. These findings imply that the time point of measuring blood loss is highly relevant, whereas the formulae applied seem to have less of an impact on the blood loss volumes calculated.

The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination - critically important issues for preclinical development and clinical translation.

Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig model.

BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

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

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

Molecular imaging of avb3 expression in cancer patients.

Angiogenesis, the formation of new blood vessels, is a key process in the growth of solid tumors. Thus this process could potentially be utilized for diagnosis of malignancies by molecular imaging on the one hand and for tumor treatment on the other hand. Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies, like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting e.g. for response assessment of such targeted antiangiogenic therapies. Several methods have been employed for imaging of angiogenesis in vivo. Mostly these approaches measure physical parameters of the tissue, e.g. blood flow, blood volume and vessel permeability. Another approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade. Integrins, like avb3, but also avb5 and a5b1, play a central role in the angiogenic process and integrin avb3 binding substances can be used as imaging probes to assess integrin expression. For clinical applications, the use of radiolabeled integrin binding substances is favorable, as radiotracers can be detected with very high sensitivities in vivo. As the radiotracer approach for molecular imaging of avb3 expression is by now the only approach used in the clinical setting, it will be the focus of this review. We will summarize the current data on imaging of avb3 expression in the clinical arena using single photon emission computed tomography (SPECT) and positron emission tomography (PET). Moreover, an outlook will be presented on potential clinical applications of imaging of avb3 expression.

[Tracers in oncology - preclinical and clinical evaluation]. / Innovative Tracer in der onkologischen Diagnostik. Präklinische und klinische Evaluierung.

UNLABELLED: In oncology, PET and PET/CT with tracers beyond FDG target more specific biological processes, such as proliferation (18F-3´-fluoro-3´-deoxy-L-thymidine; 18F-FLT), tumour hypoxia (18F-fluoromisonidazol; 18F-FMISO) and phospholipid metabolism (radioactively labelled choline derivates). FLT is a thymidine analogue which can be labelled with 18F. PET with 18F-FLT enables to non-invasively image and to quantify the proliferation fraction of tumours. Proliferation dependent accumulation of FLT has been demonstrated for a variety of solid and haematologic neoplasms including lung cancer, breast cancer, gastric cancer, colorectal cancer and malignant lymphoma. Furthermore, FLT has been suggested as surrogate marker for the assessment of response to treatment, especially when targeted drugs are utilized. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumour oxygenation. The great promise of PET/CT is its potential as a single imaging modality for whole body staging that provides anatomical and biological information on the disease as a whole. It allows a more precise estimation of the hypoxic tumour volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). PET and PET/CT with hypoxia tracers thus offer the potential to optimize and individualize therapy for patients suffering from cancer. PET- and PET/CT-studies using 11C- or 18F-labeled choline derivates recently have shown promising results for re-staging prostate cancer in patients with biochemical recurrence and advanced prostate cancer. In patients with biochemical recurrence of prostate cancer after primary therapy the detection rate of 11C-choline-PET/CT shows a positive relationship with serum PSA-levels. In these patients 11C-choline PET/CT allows not only to diagnose but also to localize recurrent disease with implications on disease management (localised vs. systemic therapy). CONCLUSION: The clinical success of multimodal imaging with PET/CT is expected to promote the combination of MRI and PET in the future.