PT  - JOURNAL ARTICLE
AU  - Jessica Lohrke
AU  - Holger Siebeneicher
AU  - Markus Berger
AU  - Michael Reinhardt
AU  - Mathias Berndt
AU  - Andre Mueller
AU  - Marion Zerna
AU  - Norman Koglin
AU  - Felix Oden
AU  - Marcus Bauser
AU  - Matthias Friebe
AU  - Ludger M. Dinkelborg
AU  - Joachim Huetter
AU  - Andrew W. Stephens
TI  - <sup>18</sup>F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi
AID  - 10.2967/jnumed.116.188896
DP  - 2017 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1094--1099
VI  - 58
IP  - 7
4099  - http://jnm.snmjournals.org/content/58/7/1094.short
4100  - http://jnm.snmjournals.org/content/58/7/1094.full
SO  - J Nucl Med2017 Jul 01; 58
AB  - 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 18F-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 18F-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: 18F-GP1 is an 18F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of 18F-GP1 to GPIIb/IIIa was 20 nM. 18F-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. 18F-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: 18F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics, 18F-GP1 is currently being investigated in a human clinical study.