Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure.

Unlabelled: Apoptosis, or programmed cell death (PCD), contributes to the decline in ventricular function in heart failure. Because apoptosis comprises a programmed cascade of events, it is potentially reversible, and timely intervention should delay the development of cardiomyopathy. (99m)Tc-Labeled annexin A5 has successfully been used for the noninvasive detection of PCD in myocardial infarction and heart transplant rejection.

Past, present, and future of annexin A5: from protein discovery to clinical applications.

In this article, we review the clinical aspects of imaging with the programmed cell-detecting protein annexin A5 (anxA5). AnxA5 binds to phosphatidylserine, which is one of the "eat me" signals at the surface of the apoptotic cell. This biologic property forms the basis for the development of anxA5 as a diagnostic tool.

Association of small fiber neuropathy with cardiac sympathetic dysfunction in sarcoidosis.

Background And Aim: Recently we found that small fiber neuropathy (SFN) occurs frequently in sarcoidosis. Autonomic dysfunction may be a feature of SFN. Since cardiac autonomic dysfunction has been identified as a strong predictor of morbidity and mortality, recognition of cardiac autonomic involvement is of clinical relevance.

The ApoCorrect assay: a novel, rapid method to determine the biological functionality of radiolabeled and fluorescent Annexin A5.

We have demonstrated that imaging of programmed cell death (PCD) in patients is possible using 99mTc-Annexin A5. Because of the short half-life of the technetium label it is important to limit the time span between the preparation of 99mTc-Annexin A5 and its administration into the patient. Therefore methods of quality control that determine the biological active fraction in the 99mTc-Annexin A5 should be not only accurate and precise but also rapid.

The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging.

Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death.

Bringing cell death alive.

The role of apoptosis in ischemia and reperfusion of the heart has been widely debated. This controversy has been continued because of the lack of an apoptosis detection method that allowed obtaining detailed kinetic and quantitative information on apoptosis. Here we focus on recent findings that look into the detection of apoptosis following ischemia and reperfusion in the heart in animal models and in patients using Annexin-A5 based image technology.

Comparison between human pharmacokinetics and imaging properties of two conjugation methods for 99mTc-annexin A5.

Annexin A5 (AnxA5) is a protein with high affinity for phosphatidyl serine, a phospholipid exposed on the cell surface during apoptosis. This phenomenon has been used for determination of cell death after myocardial infarction. To evaluate the potential of (99m)Tc-AnxA5 for in vivo scintigraphy of apoptotic cells, the pharmacokinetics and imaging properties of two radiopharmaceuticals, (99m)Tc-(n-1-imino-4-mercaptobutyl)-AnxA5 (I-AnxA5) and (99m)Tc-(4,5-bis(thioacetamido)pentanoyl)-AnxA5 (B-AnxA5), were studied.

Influence of fluid status on techniques used to assess body composition in peritoneal dialysis patients.

Objective: A reliable assessment of nutritional state in peritoneal dialysis (PD) patients is of great importance. Nevertheless, techniques used to assess body composition in patients on PD may be affected by abnormalities in fluid status. The primary aim of the present study was to compare different techniques used to evaluate body composition and to assess the influence of fluid status on the assessment of body composition.

In vivo detection of cell death in the area at risk in acute myocardial infarction.

Unlabelled: Annexin A5 is a phospholipid binding protein with high affinity for phosphatidyl-serine, which is externalized by cells undergoing programmed cell death. An increased programmed cell death rate has been reported in the heart after myocardial infarction (MI). The aim of this study was to correctly localize annexin A5 uptake in vivo and to determine the area at risk in humans with acute MI.

Assessment of fluid status in peritoneal dialysis patients.

Objectives: To assess the influence of abnormalities in fluid status and body composition on agreement between multifrequency bioimpedance analysis (MF-BIA), segmental BIA (sigmaBIA), the Watson formula, and tracer dilution techniques.

Design: Cross-sectional.

Setting: Multicenter.

Molecular imaging of cell death in intracardiac tumours: A new approach to differential diagnosis in cardiac tumours.

Background: Primary endocardial tumours are rare, but may impose a difficult clinical problem. The definite diagnosis regarding the nature of the tumour is often made after surgery. This is due to the fact that current non-invasive imaging techniques are unable to inform us about the nature of the tumour.

Visualization of cell death in vivo with the annexin A5 imaging protocol.

Annexin A5 binds to phosphatidylserine (PS), which is one of the "eat me" signals at the surface of the apoptotic cell. This property has been the driving force for the research of annexin A5 as a probe to measure apoptosis in vitro and in vivo. A non-invasive imaging protocol using annexin A5 has been developed and applied successfully to measure programmed cell death programmed cell death (PCD) in patients.

Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans.

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each.

Patient dosimetry of intravenously administered 99mTc-annexin V.

Unlabelled: Annexin V labeled with 99mTc is evaluated as a potential in vivo marker for tissue with increased apoptosis. Promising results in patients have been obtained with 99mTc-(n-1-imino-4-mercaptobutyl)-annexin V (99mTc-i-AnxV). Because information on biodistribution and radiation burden is desired for the application of any radiopharmaceutical, a dosimetric study of 99mTc-i-AnxV was undertaken.

Visualisation of cell death in vivo in patients with acute myocardial infarction.

Background: In-vivo visualisation and quantification of the extent and time-frame of cell death after acute myocardial infarction would be of great interest. We studied in-vivo cell death in the hearts of patients with an acute myocardial infarction using imaging with technetium-99m-labelled annexin-V-a protein that binds to cells undergoing apoptosis.

Methods: Seven patients with an acute myocardial infarction and one control were studied.

Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle.

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)).

Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes.

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective beta-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not significantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P<0.

Body composition in renal transplant patients: bioimpedance analysis compared to isotope dilution, dual energy X-ray absorptiometry, and anthropometry.

Whether multifrequency bioelectrical impedance analysis (MF-BIA), a relatively new method for measuring body composition, is also applicable for accurate body composition measurements in renal transplant (RTx) patients is not known. Therefore, the use of MF-BIA is validated in 77 RTx patients with a stable renal function at least 2 yr posttransplantation. MF-BIA is compared to isotope dilution techniques for measurement of body water compartments, and to dual energy x-ray absorptiometry (DEXA) and anthropometry for measurement of fat and fat free mass.

Dual-energy X-ray absorptiometry in the clinical evaluation of body composition and bone mineral density in patients with chronic obstructive pulmonary disease.

Background: Depletion of fat-free mass (FFM) occurs in a considerable number of patients with chronic obstructive pulmonary disease (COPD).

Objective: The goal of the study was to determine whether dual-energy X-ray absorptiometry (DXA) is an applicable method in the clinical evaluation of body composition in COPD.

Design: In a cross-sectional study in 79 COPD patients participating in a pulmonary inpatient program and in 23 healthy volunteers, DXA was compared with deuterium dilution (Deu) in the estimation of FFM.

Intense muscle uptake of gallium-67 in a patient with sarcoidosis.

Sarcoidosis has been associated with muscle involvement. In general, this involvement remains asymptomatic. The following case report demonstrates a patient with a 4-mo history of sarcoidosis who reported severe fatigue and slight muscular complaints at a regular checkup.

Energy expenditure and physical activity in relation to bone mineral density in women with anorexia nervosa.

Objectives: To assess sleeping metabolic rate (SMR), average daily metabolic rate (ADMR), and total bone mineral density (TBMD) in women with anorexia nervosa, and to evaluate the effect of daily physical activity on TBMD.

Design: We compared women with anorexia nervosa and controls using measurements on body composition, and energy expenditure. Relations between these measurements were investigated.

In-111 octreotide imaging in staging of small cell lung cancer.

Background: Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies have demonstrated that 50%-75% of SCLC tumors express receptors for somatostatin. This might enable in vivo localization of the primary tumor and its metastases by using scintigraphy with a radiolabeled somatostatin analogue, such as octreotide.