Klinik und Poliklinik für Nuklearmedizin

PURPOSE: Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. METHODS: An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. RESULTS: A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. CONCLUSION: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.

BACKGROUND: An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study. METHODS: Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared. RESULTS: A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a > or = 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively. CONCLUSIONS: Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.

BACKGROUND: Regular exercise in patients with stable coronary artery disease has been shown to improve myocardial perfusion and to retard disease progression. We therefore conducted a randomized study to compare the effects of exercise training versus standard percutaneous coronary intervention (PCI) with stenting on clinical symptoms, angina-free exercise capacity, myocardial perfusion, cost-effectiveness, and frequency of a combined clinical end point (death of cardiac cause, stroke, CABG, angioplasty, acute myocardial infarction, and worsening angina with objective evidence resulting in hospitalization). METHODS AND RESULTS: A total of 101 male patients aged < or =70 years were recruited after routine coronary angiography and randomized to 12 months of exercise training (20 minutes of bicycle ergometry per day) or to PCI. Cost efficiency was calculated as the average expense (in US dollars) needed to improve the Canadian Cardiovascular Society class by 1 class. Exercise training was associated with a higher event-free survival (88% versus 70% in the PCI group, P=0.023) and increased maximal oxygen uptake (+16%, from 22.7+/-0.7 to 26.2+/-0.8 mL O2/kg, P<0.001 versus baseline, P<0.001 versus PCI group after 12 months). To gain 1 Canadian Cardiovascular Society class, 6956 dollars was spent in the PCI group versus 3429 dollars in the training group (P<0.001). CONCLUSIONS: Compared with PCI, a 12-month program of regular physical exercise in selected patients with stable coronary artery disease resulted in superior event-free survival and exercise capacity at lower costs, notably owing to reduced rehospitalizations and repeat revascularizations.

UNLABELLED: Attenuation correction (AC) of whole-body PET data in combined PET/MRI tomographs is expected to be a technical challenge. In this study, a potential solution based on a segmented attenuation map is proposed and evaluated in clinical PET/CT cases. METHODS: Segmentation of the attenuation map into 4 classes (background, lungs, fat, and soft tissue) was hypothesized to be sufficient for AC purposes. The segmentation was applied to CT-based attenuation maps from (18)F-FDG PET/CT oncologic examinations of 35 patients with 52 (18)F-FDG-avid lesions in the lungs (n = 15), bones (n = 21), and neck (n = 16). The standardized uptake values (SUVs) of the lesions were determined from PET images reconstructed with nonsegmented and segmented attenuation maps, and an experienced observer interpreted both PET images with no knowledge of the attenuation map status. The feasibility of the method was also evaluated with 2 patients who underwent both PET/CT and MRI. RESULTS: The use of a segmented attenuation map resulted in average SUV changes of 8% +/- 3% (mean +/- SD) for bone lesions, 4% +/- 2% for neck lesions, and 2% +/- 3% for lung lesions. The largest SUV change was 13.1%, for a lesion in the pelvic bone. There were no differences in the clinical interpretations made by the experienced observer with both types of attenuation maps. CONCLUSION: A segmented attenuation map with 4 classes derived from CT data had only a small effect on the SUVs of (18)F-FDG-avid lesions and did not change the interpretation for any patient. This approach appears to be practical and valid for MRI-based AC.

Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.

HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca 2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca 2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P 3 (also known as LPB 3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P 3 -deficient mice, Akt phosphorylation and Ca 2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P 3mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.

Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

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.

BACKGROUND: Prevention of myocardial damage is the main goal of all reperfusion therapies in patients with acute myocardial infarction. The relative efficacy of various reperfusion strategies is under intensive investigation. We assessed whether coronary stenting combined with the blockade of platelet glycoprotein IIb/IIIa receptors produces a greater degree of myocardial salvage than fibrinolysis with an accelerated infusion of alteplase, a tissue plasminogen activator, in patients with acute myocardial infarction. METHODS: A total of 140 patients were enrolled in the randomized trial; 71 were assigned to receive a stent plus abciximab, and 69 to receive intravenous alteplase. The primary end point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium Tc 99m sestamibi. The secondary end point was a composite of death, reinfarction, and stroke within six months after randomization. RESULTS: In the group that received a stent plus abciximab, the median size of the final infarct was 14.3 percent of the left ventricle (25th and 75th percentiles, 6.8 and 24.5 percent), as compared with a median of 19.4 percent (25th and 75th percentiles, 7.9 and 34.2 percent) in the alteplase group (P=0.02). This difference was due to the larger salvage index (the percentage of the left ventricle that was salvaged, divided by the percentage that was compromised by the initial perfusion defect) in the stent group: 0.57 (25th and 75th percentiles, 0.35 and 0.69), as compared with 0.26 (25th and 75th percentiles, 0.09 and 0.61; P<0.001). The cumulative incidence of death, reinfarction, or stroke at six months was lower in the stent group than in the alteplase group (8.5 vs. 23.2 percent. P=0.02; relative risk, 0.34; 95 percent confidence interval, 0.13 to 0.88). CONCLUSIONS: In patients with acute myocardial infarction, coronary stenting plus abciximab leads to a greater degree of myocardial salvage and a better clinical outcome than does fibrinolysis with a tissue plasminogen activator.

Tinnitus is a common but poorly understood disorder characterized by ringing or buzzing in the ear. Central mechanisms must play a crucial role in generating this auditory phantom sensation as it persists in most cases after severing the auditory nerve. One hypothesis states that tinnitus is caused by a reorganization of tonotopic maps in the auditory cortex, which leads to an overrepresentation of tinnitus frequencies. Moreover, the participation of the limbic system in generating tinnitus has been postulated. Here we aimed at identifying brain areas that display structural change in tinnitus. We compared tinnitus sufferers with healthy controls by using high-resolution magnetic resonance imaging and voxel-based morphometry. Within the auditory pathways, we found gray-matter increases only at the thalamic level. Outside the auditory system, gray-matter decrease was found in the subcallosal region including the nucleus accumbens. Our results suggest that reciprocal involvement of both sensory and emotional areas are essential in the generation of tinnitus.

BACKGROUND: There have been conflicting reports of whether substantial myocardial thinning alone as an indirect sign of myocardial scarring is sufficient evidence to exclude the presence of viable myocardium in patients with previous myocardial infarction and persisting regional left ventricular akinesia. Demonstration of a dobutamine-induced contraction reserve in postischemic viable but akinetic myocardium may serve as a direct indicator of myocardial viability. In the present study, end-diastolic wall thickness at rest and dobutamine-induced systolic wall thickening assessed by magnetic resonance imaging (MRI) were compared with corresponding [18F]fluorodeoxyglucose uptake as assessed by positron emission tomography (FDG-PET). METHODS AND RESULTS: Thirty-five patients with myocardial infarction (infarct age, > 4 months) and regional akinesia or dyskinesia assessed by left ventriculography underwent rest and dobutamine MRI studies (10 micrograms dobutamine.min-1.kg-1) and FDG-PET followed by segmental analyses of end-diastolic wall thickness, systolic wall thickening, and FDG uptake in corresponding short-axis tomograms. Two definitions of viability, as assessed by MRI, of a segment akinetic at baseline were used: (1) end-diastolic wall thickness of > or = 5.5 mm (the mean minus 2.5 SD of a healthy control group [n = 21]) and (2) evidence of dobutamine-induced systolic wall thickening > or = 1 mm. Segments were graded as viable by FDG-PET if FDG uptake was > or = 50% of the maximum uptake in a region with normal wall motion as assessed by left ventriculography. Preserved end-diastolic wall thickness in akinetic regions was found in 17 of 35 (48%) patients at rest, and functional recovery within the infarct region was found in 19 of 35 (54%) patients during dobutamine infusion. Viability of the infarct region was indicated by FDG-PET in 23 of 35 patients (66%), yielding a diagnostic agreement between FDG uptake and myocardial morphology in 29 of 35 (83%) and between dobutamine-induced contraction reserve and FDG-PET in 31 of 35 (89%). Of 2200 segments, 482 (22%) were akinetic at rest. Of these akinetic segments, 234 (48%) had preserved end-diastolic wall thickness, 251 (52%) had a dobutamine-induced contraction reserve, and 299 (62%) were graded as viable by FDG-PET. Correlations of FDG uptake with end-diastolic wall thickness at rest (r = .48) and with dobutamine-induced wall thickening (r = .42) were similar. Comparison of segmental MRI and FDG-PET gradings indicated that dobutamine-induced wall thickening was a better predictor of residual metabolic activity (sensitivity, 81%; specificity, 95%; positive predictive accuracy, 96% than was end-diastolic wall thickness (sensitivity, 72%; specificity, 89%; positive predictive accuracy, 91%). However, grading a segment as viable if at least one of both MRI parameters fulfilled viability criteria improved the sensitivity (88%) of MRI for FDG-PET-assessed metabolic activity without a major decrease in specificity (87%) or positive predictive accuracy (92%). CONCLUSIONS: Viable myocardium is characterized by preserved end-diastolic wall thickness and a dobutamine-inducible contraction reserve. Both parameters should be taken into account to maximize the sensitivity of MRI in the detection of regions with signs of viability on FDG-PET images.

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1.

UNLABELLED: Technical aspects and results of the dosimetric assessments of postoperative radioiodine ablation in the framework of an international, prospective, controlled, randomized, comparative study of the effectiveness of ablation therapy with 3.7 GBq (131)I in differentiated thyroid cancer after stimulation with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are presented. METHODS: Sixty-three patients were randomized after thyroidectomy to either the THW or the rhTSH group. Scintigraphic neck images were acquired starting 48 h after radioiodine administration to assess biokinetics in the thyroid remnant. The activity in blood samples was quantified and data from whole-body probe measurements and scintigraphic whole-body scans were combined to deduce retention curves in blood and whole body, respectively. The absorbed dose to the blood was calculated using a modified approach based on the formalism of the MIRD Committee of the Society of Nuclear Medicine. RESULTS: The effective half-time in the remnant thyroid tissue was significantly longer after rhTSH than THW (67.6 +/- 48.8 vs. 48.0 +/- 52.6 h, respectively; P = 0.01), whereas the observed differences of the mean 48-h (131)I uptakes (0.5% +/- 0.7% vs. 0.9% +/- 1.0% after THW; P = 0.1) and residence times (0.9 +/- 1.3 vs. 1.4 +/- 1.5 h after THW; P = 0.1) between the rhTSH and THW groups were not statistically significant. The specific absorbed dose to the blood was significantly (P <0.0001) lower after administration of rhTSH (mean, 0.109 +/- 0.028 mGy/MBq; maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 +/- 0.061 mGy/MBq; maximum, 0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely administered after exogenous stimulation with rhTSH. CONCLUSION: Indication of an influence of the residence time of radioiodine in the blood on the fractional uptake into thyroid remnant was found. A novel regimen is proposed in which therapeutic activities to be administered are determined from the individual specific blood dose.

Gold clusters (Au55) have been shown to interact with DNA (see image). Armed with this knowledge, experiments have shown that such clusters are shown to have significant toxicity towards many types of human cells, both healthy and cancerous, in contrast to previously studied larger gold nanoparticles. It is hoped, therefore, that there is a future for Au55 clusters in the treatment of certain cancers.

OBJECTIVE: To improve the differential diagnosis between patients with multiple system atrophy (MSA) and idiopathic PD (IPD) with autonomic failure. BACKGROUND: Some patients diagnosed with IPD are discovered to have alternative diseases such as MSA, despite the application of stringent diagnostic criteria. This differentiation is particularly difficult if patients with IPD also show symptoms of autonomic failure. In IPD, autonomic failure is caused by damage of the postganglionic part of the autonomic nervous system, whereas in MSA, degeneration of preganglionic and central autonomic neurons is revealed histopathologically. METHODS: Scintigraphy with [123I]metaiodobenzylguanidine (MIBG) enables the quantification of postganglionic sympathetic cardiac innervation. Fifteen patients with IPD and 5 patients with MSA underwent standard autonomic function tests and scintigraphy with MIBG. RESULTS: In all patients, cardiovascular testing showed evidence of autonomic failure of varying severity. In all patients with IPD, the heart-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired, independent of duration and severity of autonomic and parkinsonian symptoms. All patients with MSA had a regular H/M ratio. Each patient could be assigned to the correct diagnostic group based on the results of the MIBG scintigraphy, even if the duration of the disease was only 2 years or less. CONCLUSIONS: This population assessment of the heart-mediastinum ratio of [123I]metaiodobenzylguanidine uptake showed a high sensitivity for the detection of autonomic involvement in patients with idiopathic IPD and also a high specificity for the discrimination between idiopathic PD and MSA.

BACKGROUND: Late after cardiac transplantation, limited reinnervation of the transplanted heart may occur, but little is known about the effect of reinnervation on cardiac function and exercise performance. METHODS: We quantified the extent of myocardial reinnervation noninvasively in 29 cardiac-transplant recipients, using positron-emission tomography and the catecholamine analogue [11C]hydroxyephedrine. Global and regional ventricular function at rest and during standardized exercise testing were measured with the use of radionuclide angiography, and the results were compared with those in 10 healthy controls. RESULTS: Sympathetic reinnervation, mainly in the anteroseptal wall, was present in 16 of the 29 transplant recipients. At rest, hemodynamic differences were not observed between the patients with reinnervation and those with denervation. However, the latter group had a shorter mean (+/-SD) exercise time (6.1+/-1.5, minutes vs. 8.2+/-1.2 in the group with reinnervation; P<0.01) and a lower peak heart rate (121+/-13 vs. 143+/-15 beats per minute, P<0.01). The contractile response to exercise was significantly enchanced in transplant recipients with reinnervation and similar to that of normal controls. In a multivariate analysis, hydroxyephedrine retention was the only independent determinant of the exercise-induced increase in the ejection fraction. CONCLUSIONS: In heart-transplant recipients, the restoration of sympathetic innervation is associated with improved responses of the heart rate and contractile function to exercise. These results support the functional importance of reinnervation in transplanted hearts.

In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody. Another model selection criterion, the F-test, is used for comparison. For the investigated data the corrected Akaike information criterion has proved to be an effective and efficient approach, applicable to nested and non-nested models.

BACKGROUND AND PURPOSE: Our aim was to determine the value of echo-planar diffusion-weighted MR imaging (epiDWI) in differentiating various types of primary parotid gland tumors. MATERIALS AND METHODS: One hundred forty-nine consecutive patients with suspected tumors of the parotid gland were examined with an epiDWI sequence by using a 1.5T unit. Image analysis was performed by 2 radiologists independently, and the intraclass correlation coefficient was computed. Histologic diagnosis was obtained in every patient. For comparison of apparent diffusion coefficients (ADCs), a paired 2-tailed Student t test with a Bonferroni correction was used. RESULTS: In 136 patients, a primary parotid gland tumor was confirmed by histology. Among the observers, a high correlation was calculated (0.98). ADC values of pleomorphic adenomas were significantly higher than those of all other entities, except for myoepithelial adenomas (P = .054). ADC values of Warthin tumors were different from those of myoepithelial adenomas, lipomas, and salivary duct carcinomas (P < .001, 0.013, and .037, respectively). Mucoepidermoid carcinomas, acinic cell carcinomas, and basal cell adenocarcinomas were not differentiable from Warthin tumors (P = .094, .396, and .604, respectively). CONCLUSION: epiDWI has the potential to differentiate pleomorphic adenoma and myoepithelial adenomas from all other examined entities. Due to an overlap not only within the group of benign and malignant lesions but also between groups, diagnoses should not be addressed on the basis of ADC values solely. Therefore, further studies combining DWI, morphologic criteria, and probably other MR imaging techniques seem warranted.

BACKGROUND: Coronary endothelial function and vasomotion are impaired in smokers without coronary disease, and this is thought to be due to increased oxidative stress. METHODS AND RESULTS: We used positron emission tomography to measure the coronary flow reserve, an integrated measure of coronary flow, through both the large epicardial coronary arteries and the microcirculation in 11 smokers and 8 control subjects before and after administration of the antioxidant vitamin C. At baseline, coronary flow reserve was reduced by 21% in smokers compared with control subjects (P:<0.05) but was normalized after vitamin C, whereas the drug had no effect in control subjects. CONCLUSIONS: The present study is the first to demonstrate that the noxious prooxidant effects of smoking extend beyond the epicardial arteries to the coronary microcirculation and affect the regulation of myocardial blood flow. Vitamin C restores coronary microcirculatory responsiveness and impaired coronary flow reserve in smokers, which provides evidence that the damaging effect of smoking is at least in part accounted for by an increased oxidative stress.

UNLABELLED: The aim of the study was to investigate the transport mechanism and uptake kinetics of the new 18F-labeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (L-[18F]FET) and D-[18F]FET in human SW 707 colon carcinoma cells and the in vivo biodistribution of this tracer in SW 707 tumor-bearing mice. METHODS: SW 707 cells were incubated with L- and D-[18F]FET under physiologic amino acid concentrations with and without the competitive transport inhibitors 2-amino-2 norbornane-carboxylic acid and a-(methylamino)isobutyric acid plus serine. For the investigation of the transport capacity, unlabeled L-FET was added to the samples. In addition, xenotransplanted mice were injected intravenously with L-[18F]FET; killed 10, 30, 60 and 120 min after injection; and the radioactivity concentration in different organs was measured in a gamma counter. RESULTS: The in vitro kinetic experiments showed a fast initial uptake of L-[18F]FET into the cells up to 6 min, followed by a nearly constant tracer concentration. The accumulation factor, calculated as the ratio between intracellular and extracellular tracer concentration, ranged from 3.0 to 5.0. In comparison, D-[18F]FET did not accumulate in the cells. Washing the cells in medium at 37 degrees C, after a 30-min incubation with L-[F-18]FET, led to a rapid decrease of radioactivity, which demonstrates the bidirectional transport. In addition, experiments with increasing concentrations of unlabeled L-FET indicated a linear correlation between L-FET uptake rate and the extracellular concentration. Results of transport inhibition experiments with the specific competitive inhibitors demonstrated that the uptake of L-FET into SW 707 cells was caused mainly (>80%) by the transport system L. In the in vivo studies, the half-life (t1/2 beta) of L-[18F]FET in the plasma was determined to be 94 min and the uptake into the brain increased to 120 min with a brain-to-blood ratio of 0.86. The xenotransplanted tumor showed higher uptake of L-[18F]FET (>6 %ID/g) at 30 and 60 min than all other organs, except the pancreas. The tumor-to-blood ratio reached about 2 between 30 and 120 min. CONCLUSION: L-[18F]FET, which is transported by the specific amino acid transport system L, seems to be a potential amino acid tracer for tumor imaging and therapy monitoring with PET.