Biomedical subjects

Markus Schwaiger

Publications and source records attributed to Markus Schwaiger.

At least 37 records · Page 2Linked to original sources

PubMed2006

Imaging cardiac neuronal function and dysfunction.

In recent years, the importance of alterations of cardiac autonomic nerve function in the pathophysiology of heart diseases including heart failure, arrhythmia, ische-mic heart disease, and diabetes has been increasingly recognized. Several radiolabeled compounds have been synthesized for noninvasive imaging, including single photon emission CT and positron emission tomography (PET). The catecholamine analogue I-123 metaiodobenzylguanidine (MIBG) is the most commonly used tracer for mapping of myocardial presynaptic sympathetic innervation on a broad clinical basis. In addition, radiolabeled catecholamines and catecholamine analogues are available for PET imaging, which allows absolute quantification and tracer kinetics modeling. Postsynaptic receptor PET imaging added new insights into mechanisms of heart disease. These advanced imaging techniques provide noninvasive, repeatable in vivo information of autonomic nerve function in the human heart and are promising for providing profound insights into molecular pathophysiology, monitoring of treatment, and determination of individual outcome.

Arrhythmias, Cardiac↗

PubMed2006

Recombinant P-selectin glycoprotein ligand-immunoglobulin, a P-selectin antagonist, as an adjunct to thrombolysis in acute myocardial infarction. The P-Selectin Antagonist Limiting Myonecrosis (PSALM) trial.

BACKGROUND: Inflammatory responses induced by reperfusion of previously ischemic myocardial tissue may lead to further damage of the microvascular structures. A group of cell adhesion molecules, named selectins, initiate those inflammatory changes at the endothelial wall surface. Recombinant P-selectin glycoprotein ligand-immunoglobulin (rPSGL-Ig), a P-selectin antagonist, was shown to have beneficial effects in several animal models of acute myocardial ischemia. We performed a mechanistic study with positron emission tomography to test the potential benefits of rPSGL-Ig in patients with ST-segment elevation acute myocardial infarction. METHODS: Patients with ST-elevation acute myocardial infarction presenting within the first 6 hours of onset of chest pain were enrolled. All patients received alteplase. Patients were randomly assigned in a 1:1:1 ratio to 3 treatment groups: placebo; 75 mg rPSGL-Ig; 150 mg rPSGL-Ig, given intravenously. Coronary angiography was performed 90 minutes after the start of thrombolytic therapy for TIMI flow grading. Myocardial blood flow (MBF) was measured with 13NH3 at rest and after adenosine administration on day 5. Myocardial blood flow at rest was measured again at day 30, followed by measurement of 18FDG uptake. In addition, a multigated acquisition, gated equilibrium blood pool study was performed at day 30. Continuous 12-lead electrocardiogram recording was performed during the first 24 hours. RESULTS: The trial was prematurely stopped by the sponsor for lack of efficacy in an accompanying larger trial after enrolling 88 patients in the current study. Median MBF in the infarct-related territory (expressed as percentage of the normalized blood flow) at day 5 was similar in the 3 treatment groups (9.1% in the placebo group vs 3.8% in the 75-mg dose and 4.3% in the 150-mg rPSGL-Ig treatment group; P = not significant). No significant differences in MBF reserve, myocardial metabolism, ST-segment resolution, left ventricular ejection fraction, or TIMI flow grade were found among the 3 groups. CONCLUSIONS: In this prematurely stopped mechanistic study, there was no evidence of a benefit of rPSGL-Ig given as an adjunct to thrombolysis on epicardial vessel patency, myocardial tissue reperfusion, or recovery of function.

Adolescent↗

PubMed2006

Ability of mechanical reperfusion to salvage myocardium in patients with acute myocardial infarction presenting beyond 12 hours after onset of symptoms.

BACKGROUND: The ability of primary percutaneous coronary intervention (PCI) to salvage myocardium in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting >12 hours after symptom onset is questionable. The aim of this study was to assess the ability of primary PCI to salvage myocardium in patients with STEMI presenting between 12 and 48 hours after the symptom onset. METHODS: In the BRAVE-2 trial, 365 patients with acute STEMI presenting between 12 and 48 hours from the symptom onset were randomized to an invasive (PCI) or a conservative treatment strategy. Two-hundred sixty-one patients enrolled in 2 centers had scintigraphy before randomization and 5 to 10 days later and constitute the cohort of the present study. Salvage index (proportion of initial perfusion defect salvaged) was the primary end point of this study. RESULTS: There were 131 patients randomly assigned to the invasive treatment and 130 patients assigned to the conservative treatment. Initial perfusion defect (median [25th-75th percentiles]) did not differ between groups (17.0% [9.0-28.5] vs 16.0% [9.0-37.5] of the left ventricle; P = .99). The final infarct size, measured in the follow-up scintigraphy, was significantly smaller in patients assigned to the invasive treatment than in those assigned to the conservative treatment (8.0% [2.0-16.0] vs 12.0% [3.2-25.0] of the left ventricle; P = .004). Salvage index was 0.44 (0.13-0.80) in the invasive group versus 0.23 (0.0-0.50) in the conservative group (P < .001). CONCLUSION: Primary PCI leads to significant myocardial salvage in patients with STEMI presenting between 12 and 48 hours after symptom onset.

Aged↗

PubMed2006

Chemoselective hydrazone formation between HYNIC-functionalized peptides and (18)F-fluorinated aldehydes.

INTRODUCTION: Since the demand for (18)F-fluorinated peptides for quantitative in vivo receptor imaging using PET has increased, a new chemoselective two-step (18)F-labeling strategy based on hydrazone formation between an unprotected hydrazine-functionalized peptide and an (18)F-labeled aldehyde was developed. METHODS: First, 4-[(18)F]fluorobenzaldehyde ([(18)F]FB-CHO) was prepared from 4-formyl-N,N,N-trimethylanilinium triflate via direct no-carrier-added (18)F-fluorination (dimethyl sulfoxide, 90 degrees C, 5 min) and purified by RP-HPLC. Hydrazone formation between [(18)F]FB-CHO and 6-hydrazinonicotinic acid (HYNIC) and the unprotected HYNIC-functionalized peptides (HYNIC-d-Phe(1))-Tyr(3)-Thr(8)-octreotide and (HYNIC-Arg(1))-substance P was evaluated with respect to the dependence of radiochemical yield on pH, precursor concentration and temperature. The stability of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)(NH(2))-octreotide in aqueous solution at various pH (4.0, 5.5 and 7.5) as well as the in vivo stability of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)-octreotide in mouse blood (30 min p.i.) was investigated. RESULTS: Yields of the hydrazone formation were independent of pH between pH 0.5 and 5.5. Optimal labeling yields of 85% were obtained with a precursor concentration of 2.1 mM at 70 degrees C for 10 min. The labeling products were stable at pH 7.5 at 37 degrees C, while in more acidic media (pH 4.0) the product slowly decomposed to form up to 31+/-2% [(18)F]FB-CHO within 5 h. Metabolite studies showed no detectable degradation of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)-octreotide in mouse blood (30 min p.i.). CONCLUSIONS: In conclusion, chemoselective hydrazone formation between unprotected HYNIC-functionalized peptides and [(18)F]FB-CHO is a fast and straightforward radiolabeling method leading to high yields under mild acidic conditions. In addition, it represents a powerful and versatile radiolabeling strategy that is applicable to a variety of radionuclides and peptide precursors already available for (99m)Tc labeling.

Aldehydes↗

PubMed2006

Gluc-Lys([18F]FP)-TOCA PET in patients with SSTR-positive tumors: biodistribution and diagnostic evaluation compared with [111In]DTPA-octreotide.

UNLABELLED: A recently developed (18)F-labeled PET tracer for somatostatin receptor (sstr) imaging, N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate (Gluc-Lys([(18)F]FP)-TOCA), was evaluated in patients with sstr-positive tumors by assessing the pharmacokinetics, biodistribution, and diagnostic performance in comparison with [(111)In]DTPA-octreotide. METHODS: Twenty-five patients with different sstr-positive tumors were included in the study and were injected with 105 +/- 50 MBq Gluc-Lys([(18)F]FP)-TOCA. PET was performed up to 120 min with 2 different dynamic imaging protocols. Tracer kinetics in tumors and nontumor tissues and tumor-to-background ratios were described by region-of-interest analysis and standardized uptake values (SUVs). In 16 patients, sstr scintigraphy with [(111)In]DTPA-octreotide was performed (whole-body scans and SPECT). Two independent experts on PET and gamma- camera scans performed lesion counts. RESULTS: Gluc-Lys([(18)F]FP)-TOCA showed a fast and intense tumor accumulation as well as a rapid clearance from blood serum (biexponential elimination, with the half-lives of the initial and the terminal elimination phase calculated as t(1/2)(1) = 2.3 +/- 1.3 min and t(1/2)(2) = 26.4 +/- 14.6 min, respectively). Tumor-to-background ratios at 16 +/- 9 min and 34 +/- 12 min were as high as 80% and 90% (% of maximum ratios), respectively. Tumors showed high SUVs ranging from 13.7 +/- 2.3 (tumors in lung) up to 26.9 +/- 15.4 (abdominal tumors). Tracer distribution within tumor and nontumor tissues was stable up to 120 min (except spleen). No significant bowel activity was observed. Comparison of 29 tumors located in the liver showed a mean tumor-to-background ratio of 5.3 +/- 2.6 for Gluc-Lys([(18)F]FP)-TOCA vs. 4.6 +/- 3.3 for [(111)In]DTPA-octreotide (P = 0.24). Visual image analysis revealed a significantly higher number of lesions (factor of 2.4) and improved interobserver correlation (r = 0.99 vs. 0.86) for PET. CONCLUSION: Gluc-Lys([(18)F]FP)-TOCA PET allows a fast, high- contrast imaging of sstr-positive tumors. The biokinetics and diagnostic performance of Gluc-Lys([(18)F]FP)-TOCA are superior to [(111)In]DTPA-octreotide and-as far as can be derived from the literature-comparable with [(68)Ga]-DOTA-d Phe(1)-Tyr(3)-octreotide ([(68)Ga]DOTATOC).

Adult↗

PubMed2006

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

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

Adult↗

PubMed2006

Value of 11C-choline PET and contrast-enhanced CT for staging of bladder cancer: correlation with histopathologic findings.

UNLABELLED: Lymph node involvement is a major prognostic factor in bladder cancer, but the accuracy of conventional imaging modalities for the prediction of regional and distant metastatic diseases is limited. This study was performed to compare the diagnostic accuracies of contrast-enhanced CT and PET with (11)C-choline for the staging of urothelial bladder cancer. METHODS: Twenty-seven patients (median age, 69.1 y) who had urothelial bladder cancer and who were referred for radical cystectomy and pelvic lymph node dissection (PLND) on the basis of a histologic evaluation after transurethral resection of bladder cancer (TURB) were studied. PET scanning, using 2 multiring whole-body tomographs, was performed 5 min after intravenous injection of approximately 370-500 MBq of (11)C-choline. In addition, conventional bone scintigraphy and contrast-enhanced CT were performed. After imaging, cystectomy and PLND were performed in all patients. Pathologic (11)C-choline uptake that could not be explained by intestinal activity was noted as a positive result. Node positivity was determined by size on CT: nodes measuring more than 1 cm in the long axis were described as being positive for tumor. Histopathologic findings were used as a reference. RESULTS: The presence of residual bladder cancer (pTa-pT4) was correctly detected in 21 of 25 histologically tumor-positive patients (84%) by CT and in 24 of 25 patients (96%) by (11)C-choline PET. Lymph node involvement was correctly detected in 4 of 8 patients (50%) by CT and in 5 of 8 patients (62%) by (11)C-choline PET. The median size of the 3 nodes with false-negative PET results was 9 mm (range, 6-21 mm), and the median size of the metastatic lesions within the lymph nodes was 3 mm (range, 1-15 mm). CT resulted in 6 (22%) false-positive lymph nodes, whereas none was demonstrated by (11)C-choline PET; these data indicated a significantly higher accuracy of PET than of CT (P < 0.01). Both modalities missed a small peritoneal metastasis verified by histologic evaluation. No positive results were obtained from bone scintigraphy. CONCLUSION: These preliminary data suggest that (11)C-choline PET is comparable to CT for detecting residual bladder cancer after TURB but appears to be superior to CT for the evaluation of potential additional lymph node metastases. (11)C-choline PET should be further evaluated for staging in patients who have bladder cancer and who are scheduled for radical cystectomy.

Aged↗

PubMed2006

Effect of diabetes mellitus on sympathetic neuronal regeneration studied in the model of transplant reinnervation.

UNLABELLED: The transplanted heart is initially denervated but undergoes subsequent sympathetic reinnervation. It thus provides a unique model for studying regeneration as a specific component of autonomic nerve biology. The aim of this study was to determine the effect of diabetes mellitus on the regenerational capacity of sympathetic neurons using molecule-targeted PET. METHODS: Twenty-two nonrejecting, otherwise healthy cardiac transplant recipients underwent PET with the (11)C-labeled physiologic neurotransmitter epinephrine at 4.0 +/- 3.3 y after surgery. Sympathetic reinnervation was defined as regional restoration of epinephrine retention to values within normal limits. RESULTS: Reinnervation was observed in 8 of 12 patients with no evidence of diabetes and in 6 of 10 patients with a long-term history of diabetes mellitus. The regional extent of reinnervation (4.7% +/- 5.3% of left ventricle vs. 19.1% +/- 20.6% for nondiabetic recipients, P = 0.04) and the regeneration rate (0.8% +/- 1.0% of left ventricle per year vs. 8.0% +/- 10.1% for nondiabetic recipients, P = 0.04) were significantly reduced in diabetic subjects. In a multivariate model, diabetes mellitus was an independent determinant of allograft reinnervation. Finally, the reappearance of innervation was found to correlate with an improved chronotropic and inotropic response to stress in a standardized, symptom-limited exercise test including radionuclide angiography. CONCLUSION: The regenerational capacity of the sympathetic nervous system of the heart is reduced, but not abolished, by diabetes mellitus. This study on cardiac transplant recipients further supports a general link between impaired glucose handling and cardiac autonomic nerve function.

Catecholamines↗

PubMed2005

Syntheses, biological evaluation, and molecular modeling of 18F-labeled 4-anilidopiperidines as mu-opioid receptor imaging agents.

The synthesis, evaluation, and molecular modeling of a series of 18F-labeled 4-anilidopiperidines with high affinities for the mu-opioid receptor (mu-OR) are reported. On the basis of the high brain uptake and selective retention in brain regions that contain a high concentration of the mu-OR, combined with a good metabolic stability, [18F]fluoro-pentyl carfentanil ([18F]4) and 2-(+/-)[18F]fluoropropyl-sufentanil ([18F]6) were selected as the lead compounds for further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM for [18F]4 and [18F]6, respectively. In vitro autoradiography of [18F]4 and [18F]6 on rat brain sections produced patterns in accordance with the known distribution of mu-OR expression. Structure-activity relationships of the fluorinated compounds are discussed with respect to the interaction with an activated-state model of the mu-OR. Taken together, the in vivo and in vitro data indicate that [18F]4 and [18F]6 hold promise for studying the mu-opioid receptor in humans by means of positron emission tomography.

Aniline Compounds↗

PubMed2005

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

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

Adult↗

PubMed2005

Fractionated locoregional low-dose radioimmunotherapy improves survival in a mouse model of diffuse-type gastric cancer using a 213Bi-conjugated monoclonal antibody.

PURPOSE: Locoregional radioimmunotherapy of i.p. tumor cell dissemination of diffuse-type gastric cancer using the alpha-emitter 213Bi displayed good therapeutic results after a single application depending on the time interval between tumor cell inoculation and injection of the 213Bi-immunoconjugate. The aim of the present study was to compare single versus double i.p. injection of a tumor-specific antibody (d9MAb) conjugated with low activities of 213Bi in terms of therapeutic efficacy and toxicity. EXPERIMENTAL DESIGN: Nude mice were inoculated i.p. with 1 x 10(7) human gastric cancer cells (HSC45-M2) expressing tumor-specific mutant d9-E-cadherin (d9-E-cad). After tumor cell inoculation, the mice were injected i.p. with a single injection at day 1 or 8, or double injections at days 1 and 8 or days 8 and 15 with 0.37, 0.74, or 1.48 MBq 213Bi-d9MAb. Therapeutic efficacy was determined by median survival, and toxicity was evaluated by leukocyte and platelet counts. The development of i.p. carcinomatosis was monitored by carcinoembryonic antigen concentrations in the serum of the mice. RESULTS: The median survival of treated animals increased, depending on the time interval (days) between tumor cell inoculation and therapy, and the injected activity, from 22 days of untreated mice to 48 days (0.37 MBq, 1 day), 84 days (0.37 MBq, 1 and 8 days), 37 days (0.37 MBq, 8 days), 46 days (0.37 MBq, 8 and 15 days), 42 days (0.74 MBq, 8 days), 78 days (0.74 MBq, 8 and 15 days), and 44 days (1.48 MBq, 8 days). The injected activities did not reduce leukocyte and platelet counts. Carcinoembryonic antigen, which was not detectable in the serum of tumor-free mice, increased after tumor cell inoculation and tumor proliferation and decreased after each therapeutic application of 213Bi-d9MAb. CONCLUSIONS: Double application of only 0.37 MBq of 213Bi-d9MAb at days 1 and 8 after tumor cell inoculation significantly prolonged median survival in nude mice suffering from i.p. tumor cell dissemination compared with a single injection. Even in an advanced stage of the disease, double injection of 0.74 MBq at days 8 and 15 was superior to a single injection of 1.48 MBq at day 8 without any sign of toxicity.

Animals↗

PubMed2005

Impaired cross-modal inhibition in Alzheimer disease.

BACKGROUND: Successful cognitive performance depends not only on the activation of specific neuronal networks but also on selective suppression of task-irrelevant modalities, i.e., deactivation of non-required cerebral regions. This ability to suppress the activation of specific brain regions has, to our knowledge, never been systematically evaluated in patients with Alzheimer disease (AD). The aim of the current study was to evaluate both cerebral activation and deactivation in (1) healthy volunteers, (2) patients with mild cognitive impairment (MCI) who are at risk for AD, and (3) patients with moderate AD during active navigation, representing a cognitive task typically affected in AD. METHODS AND FINDINGS: Changes in regional cerebral blood flow (rCBF) were assessed with PET imaging during an active navigation task in a 3D virtual-reality environment. The task was based on visual cues exclusively; no auditory cues were provided. Age-matched groups of healthy individuals, patients with MCI, and patients with AD were examined. Specific differences in the activation patterns were observed in the three groups, with stronger activation of cerebellar portions and visual association cortex in controls and stronger activation of primary visual and frontal cortical areas in patients with MCI and AD. Highly significant bilateral decrease of rCBF in task-irrelevant auditory cortical regions was detected in healthy individuals during performance of the task. This rCBF decrease was interpreted as a cross-modal inhibitory effect. It was diminished in patients with MCI and completely absent in patients with AD. A regression analysis across all individuals revealed a clear positive relation between cognitive status (mini mental state examination score) and the extent of auditory cortical deactivation. CONCLUSION: During active navigation, a high level of movement automation and an involvement of higher-order cerebral association functions were observed in healthy controls. Conversely, in patients with MCI and AD, increased cognitive effort and attention towards movement planning, as well as stronger involvement of lower-order cerebral systems, was found. Successful cognitive performance in healthy individuals is associated with deactivation of task-irrelevant cerebral regions, whereas the development of AD appears to be characterized by a progressive impairment of cross-modal cerebral deactivation functions. These changes may cause the generally decreased ability of patients with AD to direct attention primarily to the relevant cognitive modality.

Aged↗

PubMed2005

Changes in myocardial vasoreactivity after drastic reduction of plasma fibrinogen and cholesterol: a clinical study in long-term heart transplant survivors using positron emission tomography.

BACKGROUND: Given the central importance of the microvasculature in heart transplant recipients, we investigated the possibility of increasing cardiac perfusion after reduction of low-density lipoprotein (LDL)-cholesterol, lipoprotein (a), C-reactive protein (CRP) and fibrinogen plasma levels after apheresis treatment in transplanted patients. METHODS: Ten long-term heart transplant recipients were examined with positron emission tomography (PET) to measure myocardial perfusion before and after a single heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP)-apheresis treatment. PET studies were performed the mornings before and after the apheresis treatment. Myocardial blood flow at rest and during adenosine-induced hyperemia was measured using (13)N-ammonia. RESULTS: HELP-apheresis reduced the plasma levels of LDL-cholesterol, lipoprotein (a) and C-reactive protein by 48% (p < 0.001), fibrinogen by 42% (p = 0.02), plasma viscosity by 14% (p = 0.004) and erythrocyte aggregation by 28% (p < 0.02). Osmolality (<1%) and hematocrit (<2%) remained stable. A single apheresis treatment increased median corrected rest flow by 17.5% (p = 0.007) and median hyperemic flow by 27% (p = 0.02). Median coronary flow reserve increased by 8.1% (p = 0.09). Hyperemic flow after adenosine infusion increased plasma vascular endothelial growth factor levels only before HELP-apheresis (+60%), indicating better ischemic tolerance after apheresis (p = 0.01). CONCLUSIONS: Myocardial perfusion in transplanted hearts increases significantly after single HELP-apheresis treatment. The present study is only a proof of concept, providing complementary evidence to clinical long-term studies showing that cholesterol reduction either with statins and/or apheresis improves heart transplant outcome.

Anticoagulants↗

PubMed2005

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

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

Adult↗

PubMed2005

[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide.

PURPOSE: Scintigraphy with maltotriose-[123I]Tyr3-octreotate ([123I]Mtr-TOCA) is compared with [111In]DTPA-Phe1-octreotide ([111In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [131I]Mtr-TOCA. METHODS: Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137 +/- 28 MBq [123I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [111In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed. RESULTS: [123I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [111In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [111In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [123I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [111In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9 +/- 0.9 mSv per 100 MBq [123I]Mtr-TOCA. CONCLUSION: Compared with [111In]OC, [123I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [123I]Mtr-TOCA and [111In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention

Humans↗

PubMed2005

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

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

Adult↗

PubMed2005

Fixation suppression of optokinetic nystagmus modulates cortical visual-vestibular interaction.

Water activation positron emission tomography and statistical group analysis were used to evaluate differences in activation-deactivation patterns during small-field visual motion stimulation, eliciting rightward optokinetic nystagmus and its fixation suppression in 12 healthy volunteers. Bilateral patterns of activation in the visual cortex, including the motion-sensitive area MT/V5, and deactivations in an assembly of vestibular areas (posterior insula, thalamus, anterior cingulate gyrus) during optokinetic nystagmus was markedly diminished or totally absent during its fixation suppression. This finding agrees with the concept of a reciprocal inhibitory interaction between the visual-optokinetic and the vestibular systems, which takes place at a lower level during fixation suppression, because the potential mismatch between the two sensory inputs, visual and vestibular, is then reduced.

Adult↗

PubMed2005

Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial.

CONTEXT: No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. OBJECTIVE: To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. DESIGN, SETTING, AND PATIENTS: International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset. INTERVENTIONS: Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183). MAIN OUTCOME MEASURES: The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days. RESULTS: The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was -6.8% (95% confidence interval [CI], -10.2% to -3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37). CONCLUSION: An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.

Abciximab↗