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Query: UMLS:C0034065 (
pulmonary embolism
)
14,979
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and
pulmonary embolism
are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (
GPIIb
/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to
GPIIb
/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches.
Methods:
Binding of
18
F-GP1 to
GPIIb
/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for
18
F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta.
Results:
18
F-GP1 is an
18
F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of
18
F-GP1 to
GPIIb
/IIIa was 20 nM.
18
F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin.
18
F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging.
Conclusions:
18
F-GP1 binds specifically with high affinity to the
GPIIb
/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics,
18
F-GP1 is currently being investigated in a human clinical study.
...
PMID:
18
F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi. 2908 26
Thrombus formation can lead to heart attacks, stroke and
pulmonary embolism
, which are major causes of mortality. Current standard diagnostic imaging methods detect anatomic abnormalities such as vascular flow impairment but have limitations. By using a targeted molecular imaging approach critical components of a pathology can be selectively visualized and exploited for an improved diagnosis and patient management. The
GPIIb
/IIIa receptor is abundantly and specifically exposed on activated platelets and is the key receptor in thrombus formation. This commentary describes the current status of
GPIIb
/IIIa-based PET imaging approaches with a focus on the recently published preclinical data of the small-molecule PET tracer
18
F-GP1. Areas of future research and potential clinical applications are discussed that may lead to an improved detection of critical thromboembolic events and an optimization of available antithrombotic therapies by tracking activated platelets.
...
PMID:Commentary to
18
F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi: Imaging Activated Platelets in Clots-Are We Getting There? 2790 Oct 92
Thrombotic disorders are characterized by an increase in the probability of the formation of unnecessary thrombi that might be due to the activation of the coagulation cascade or the circulating platelets. Platelets or thrombocytes play an essential role in hemostasis but abnormal platelet function leads to the development of a number of cardiovascular complications, including thrombotic disorders. Under pathological conditions, platelets are associated with the development of different thrombotic disorders, including atherosclerosis, arterial thrombosis and stroke, deep venous thrombosis and
pulmonary embolism
; therefore, platelets are the target of a number of anti-thrombotic strategies. Flavonoids, a large group of polyphenols ubiquitously expressed in fruits and vegetables that have attracted considerable attention because of their benefits in human health, including the reduction of the risk of cardiovascular disease. Flavonoids have been reported to reduce platelet activity by attenuating agonist-induced
GPIIb
/IIIa receptor activation, mobilization of intracellular free Ca2+, granule exocytosis, as well as activation of different signaling molecules such as mitogen- activated protein kinases or phospholipases. This review summarizes the current studies concerning the modulation of platelet activation by flavonoids, giving especial attention to those events associated to thrombotic disorders.
...
PMID:Flavonoids and Platelet-Derived Thrombotic Disorders. 2966 48
Patients with schizophrenia are predisposed toward developing cardiovascular disease. Although neuroleptics affect the cardiovascular system, it is also important to consider the consequences of the disease itself such as lower physical activity due to living on disability pension, inadequate nutrition, and/or nicotine addiction, being more common among patients with schizophrenia versus the general population. All these factors combined lead to an increased risk of death caused by cardiovascular conditions in schizophrenic patients. Individuals receiving typical antipsychotic drugs have been reported to have elevated concentrations of antiphospholipid antibodies, including anticoagulants and anticardiolipin antibodies. The presence of both antibodies is associated with an increased risk for thromboembolism. It is also likely that mental illness is accompanied by increased procoagulant activity. Patients with acute psychosis have been shown to have a statistically significant increase in the concentrations of D-dimer, P-selectin, and in the expression of
platelet glycoprotein IIb
/IIIa receptors. Learning about causes and mechanisms of venous thromboembolism could help to reduce or neutralize the adverse effects of antipsychotic treatment and facilitate the identification of appropriate markers necessary to monitor changes and provide preventive care against hazardous and potentially fatal complications such as deep venous thrombosis and
pulmonary embolism
. Before atypical neuroleptic treatment is administered to hospitalized patients, all possible risk factors for thromboembolism should be considered to allow the application of lower risk drugs. Also, other preventive measures should be taken into account, including hydration, compression stockings, regular exercise of lower extremities, and low-molecular-weight heparin injections.
...
PMID:The impact of antipsychotics as a risk factor for thromboembolism. 2967 40
18
F-GP1 is a derivative of elarofiban with a high affinity to activated
platelet glycoprotein IIb
/IIIa (
GPIIb
/IIIa) and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with
18
F-GP1 positron emission tomography/computed tomography (PET/CT) in patients with acute venous thromboembolism (VTE), and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of
18
F-GP1.
Methods:
We studied patients who had signs or symptoms of acute deep vein thrombosis (DVT) of the leg or acute
pulmonary embolism
(PE) within 14 days prior to
18
F-GP1 PET/CT, and had thromboembolic foci confirmed by conventional imaging (
n
= 10 for DVT and
n
= 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140 minutes after injection of 250 MBq of
18
F-GP1.
Results:
18
F-GP1 PET/CT was well tolerated without any drug-related adverse events, and showed high initial uptake in spleen, kidney, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients.
18
F-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that
18
F-GP1 PET/CT detected 89% (68/76) of vessels with DVT, and 60% (146/245) for PE. Importantly,
18
F-GP1 PET/CT showed increased uptake in 32 vessels that were not detected by conventional imaging, of which 25 were located in distal veins of the lower extremity in 12 patients. A positive correlation was found between
18
F-GP1 uptake and P-selectin-positive circulating platelets (
r
= 0.656,
P
= 0.002).
Conclusion:
18
F-GP1 is a promising PET tracer for imaging acute VTE in patients.
18
F-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.
...
PMID:Glycoprotein IIb/IIIa receptor imaging with
18
F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study. 2995 14
Venous thrombosis leads to severe symptoms and death through
pulmonary embolism
. There is a great need for high sensitivity imaging methods to identify acute patients who would benefit from thrombolysis. We designed a novel, organic near-infrared second-window (NIR-II) probe, which targets the glycoprotein IIb/IIIa receptor (
GPIIb
/IIIa) on activated platelets. The probe's structure was characterized by MALDI-TOF-MS, TEM, UV-visible absorption and NIR-II fluorescent spectroscopy. The probe's specificity for activated platelets was investigated in vitro and in vivo. Thrombosis in mice was induced by administration of FeCl
3
in the external jugular vein and imaged by using a NIR-II imager. The donor-acceptor-donor fluorescent core TTQ was prepared from donor and acceptor units. TTQ-PEG-NH
2
was synthesized by sequential modification of PEGylated TTQ, followed by c(RGD) condensation. Signal strength was continuously monitored for 24 h following TTQ-PEG-c(RGD) or non-specific fluorescent dye injection. The contralateral external jugular vein, sham surgery and a competitive inhibition experiment served as controls. TTQ-PEG-c(RGD) presented high NIR-II intensity, good stability and excellent affinity for activated platelets. The NIR-II fluorescence signal of TTQ-PEG-c(RGD) injected mice significantly increased at the thrombus site and peaked at 4 h, whereas there was no significant change in the control mice, and the competitive inhibition of the RGD antagonist suppressed the enhancement of the NIR-II fluorescence signal. Comparison between fresh and old thrombi confirmed that TTQ-PEG-c(RGD) could be used to distinguish a fresh thrombus from an old thrombus. TTQ-PEG-c(RGD) can specifically target thrombosis in vitro and in vivo, providing a potential tool for noninvasive diagnosis of early thrombi.
...
PMID:An RGD modified water-soluble fluorophore probe for in vivo NIR-II imaging of thrombosis. 3264 82
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