Atherosclerotic plaque uptake of a novel integrin tracer 18F-Flotegatide in a mouse model of atherosclerosis

• Published in: Journal of nuclear cardiology Vol. 21; no. 3; pp. 553 - 562
• Main Authors: Su, Helen, Gorodny, Natalia, Gomez, Luis Felipe, Gangadharmath, Umesh B., Mu, Fanrong, Chen, Gang, Walsh, Joseph C., Szardenings, Katrin, Berman, Daniel S., Kolb, Hartmuth C., Tamarappoo, Balaji K.
• Format: Journal Article
• Language: English
• Published: Boston Elsevier Inc 01.06.2014; Springer US
• Subjects: angiogenesis; Animals; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - diagnostic imaging; Atherosclerosis - metabolism; Biomarkers - metabolism; Cardiology; Disease Models, Animal; Female; Fluorine Radioisotopes - pharmacokinetics; Imaging; inflammation; Integrin alphaVbeta3 - metabolism; integrin αvβ3; Medicine; Medicine & Public Health; Mice; Mice, Knockout; Molecular Imaging - methods; Nuclear Medicine; Oligopeptides - pharmacokinetics; Original Article; PET; Positron-Emission Tomography - methods; Radiology; Radiopharmaceuticals - pharmacokinetics; Reproducibility of Results; Sensitivity and Specificity; integrin αvβ3; inflammation; angiogenesis; PET; Atherosclerosis
• ISSN: 1071-3581; 1532-6551
• DOI: 10.1007/s12350-014-9879-3

Rupture of unstable atherosclerotic plaque that leads to stroke and myocardial infarction may be induced by macrophage infiltration and neovessel formation. A tracer that selectively binds to integrin αvβ3 a protein expressed by macrophages and neovascular endothelium may identify rupture prone plaque. 18F-labeled “R-G-D” containing tripeptide (Flotegatide), a click chemistry derived radiotracer that binds to integrin αvβ3 was injected in ApoE knockout mice fed a high fat diet. Uptake of Flotegatide by atherosclerotic plaque was visualized by micro-PET, autoradiography, and correlated to histologic markers of inflammation and angiogenesis. We found that Flotegatide preferentially binds to aortic plaque in an ApoE knockout mouse model of atherosclerosis. The tracer’s uptake is strongly associated with presence of histologic markers for macrophage infiltration and integrin expression. There is a weaker but detectable association between Flotegatide uptake and presence of an immunohistochemical marker for neovascularization. We hypothesize that Flotegatide may be a useful tracer for visualization of inflamed plaque in clinical subjects with atherosclerosis and may have potential for detecting vulnerable plaque.