Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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
