sodium-pertechnetate-tc-99m and Reperfusion-Injury

P-selectin expression is involved in the pathophysiology of biologically active arterial thrombus and endothelial activation after a transient ischemic event. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In the present study, we propose a new approach of P-selectin molecular imaging based on radiolabeled fucoidan.. Two kinds of experimental models were selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin expression: platelet-rich arterial thrombi (vegetations of infective endocarditis and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2 settings were chosen because they were clinically relevant, and both were associated with an important overexpression of platelet and endothelial P-selectin, respectively.. (99m)Tc-fucoidan SPECT was able to detect the presence of platelet-rich arterial thrombi in all animals, with a median target-to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h after reperfusion. In this latter model, the magnitude of the signal was correlated with the extent of myocardium that underwent transient ischemia. The sensitivity of selectivity of the uptake and retention of (99m)Tc-fucoidan in both settings was excellent.. This study supports (99m)Tc-fucoidan as a relevant imaging agent for in vivo detection of biologic activities associated with P-selectin overexpression, such as arterial thrombus and ischemic memory. Given the reported wide availability at a low cost, and its low toxicity, fucoidan seems to overcome some of the limitations of previous P-selectin-targeted imaging agents.

Topics: Animals; Annexin A5; Aortic Aneurysm, Abdominal; Aortic Valve; Autoradiography; Blood Platelets; Endocarditis, Bacterial; Endothelium, Vascular; Immunohistochemistry; In Vitro Techniques; Ischemia; Isotope Labeling; Male; P-Selectin; Polysaccharides; Radiopharmaceuticals; Rats; Rats, Inbred Lew; Rats, Wistar; Reperfusion Injury; Sodium Pertechnetate Tc 99m; Thrombosis; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

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.. Seven patients with an acute myocardial infarction and one control were studied. All patients were treated by percutaneous transluminal coronary angioplasty (six primary and one rescue), resulting in thrombolysis in myocardial infarction (TIMI) III flow of the infarct-related artery. 2 h after reperfusion, 1 mg annexin-V labelled with 584 MBq Tc-99m was injected intravenously. Early (mean 3.4 h) and late (mean 20.5 h) single-photon-emission computed tomographic (SPECT) images of the heart were obtained. Routine myocardial resting-perfusion imaging was also done to verify infarct localisation.. In six of the seven patients, increased uptake of Tc-99m-labelled annexin-V was seen in the infarct area of the heart on early and late SPECT images. No increased uptake was seen in the heart outside the infarct area. All patients with increased Tc-99m-labelled annexin-V uptake in the infarct area showed a matching perfusion defect. In a control individual, no increased uptake in the heart was seen.. Increased uptake of Tc-99m-labelled annexin-V is present in the infarct area of patients with an acute myocardial infarction, suggesting that programmed cell death occurs in that area. The annexin-V imaging protocol might allow us to study the dynamics of reperfusion-induced cell death in the area at risk and may help to assess interventions that inhibit cell death in patients with an acute myocardial infarction.

Topics: Aged; Angioplasty, Balloon, Coronary; Annexin A5; Apoptosis; Cell Death; Coronary Circulation; Coronary Vessels; Female; Follow-Up Studies; Heart; Humans; Image Processing, Computer-Assisted; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Myocardium; Organophosphorus Compounds; Organotechnetium Compounds; Protein Binding; Radiopharmaceuticals; Reperfusion Injury; Sodium Pertechnetate Tc 99m; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aortic Diseases; Capillary Permeability; Citrates; Citric Acid; Erythrocytes; Female; Gallium Radioisotopes; Humans; Inflammation Mediators; Interleukin-8; Lung; Male; Middle Aged; Neutrophil Activation; Peptidyl-Dipeptidase A; Peripheral Vascular Diseases; Postoperative Complications; Radionuclide Imaging; Reperfusion Injury; Respiratory Distress Syndrome; Sodium Pertechnetate Tc 99m