^99m Tc-Annexin-V Functional Imaging of Luminal Thrombus Activity in Abdominal Aortic Aneurysms

Abstract

Background-The mural thrombus of abdominal aortic aneurysms (AAA) is involved in aneurysm progression via several interdependent biological processes including platelet activation. 99m Tc-annexin V (ANX) is a scintigraphic tracer that binds to phosphatidylserine exposed on activated platelets and apoptotic cells. Here, we evaluated the potential of ANX imaging to assess mural thrombus biological activity in an experimental AAA model. The clinical applicability was further tested ex vivo on human samples of excised AAA thrombi. Methods and Results-Experimental AAA was created by infusing elastase into infrarenal abdominal aorta in 17 rats, and 6 sham-operated rats were used as controls. Abdominal ANX scintigraphy was performed 2 weeks later followed by quantitative autoradiography and histological studies. Among the 13 rats which developed AAA, 11 displayed intense ANX uptake within AAA by scintigraphy. ANX uptake in the aneurysms on planar and single-photon emission computed tomography (SPECT) imaging was higher than that observed in infrarenal aorta of sham-operated controls (target/background ratio: 5.7Ϯ0.9 versus 1.33Ϯ0.21; PϽ0.005 for SPECT). Aneurysm-to-background activity ratios obtained by scintigraphy correlated with ANX activity in corresponding autoradiograms (Rϭ0.69; PϽ0.02). This activity was located in the thrombus area where activated platelets and polymorphonuclear leukocytes accumulated. Similar patterns were also found in all of the 7 human AAA thrombi harvested during surgery. Conclusions-ANX imaging may assess mural thrombus renewal activity linked to permanent flowing blood interface.

Technetium 99m–Labeled Annexin V Scintigraphy of Platelet Activation in Vegetations of Experimental Endocarditis

“…As proposed by some authors 5 and shown in the present study, nonbacterial and bacterial thrombotic endocarditis share common pathological consequences, mainly linked to platelet procoagulant 22,32 and proteolytic activities conveyed by thrombus formation and degradation, 12 which are greatly amplified by biological activities conveyed by the bacteria themselves. 11,33 Therefore, whatever their predominant source, platelet proaggregant and procoagulant activities participate in the development of vegetations, fibrinolytic activities contribute to sepsis diffusion and embolic potential, and numerous proteases are involved in tissue destruction in relation to their ability to damage extracellular matrix and to induce cell death.…”

“…13,15,37 Thus, radiolabeled annexin V has been used previously for in vivo scintigraphy of apoptotic cells in both animals and humans 16 -19 and acute platelet-rich 20,21 or chronically renewed mural thrombi, maintaining a permanent interface with the circulating blood. 22 Therefore, exposed phosphatidylserines can be targeted by Tc-ANX binds to and allows in vivo detection of right-and left-sided thrombotic vegetations in experimental endocarditis. Superposition of autoradiography and corresponding histological section showed that, as in the aseptic mural thrombus in abdominal aortic aneurysms, 22 annexin V predominantly binds to the most luminal layer of the vegetation, corresponding to the dynamic biologically active interface between the circulating blood components and the vegetation.…”

“…22 Therefore, exposed phosphatidylserines can be targeted by Tc-ANX binds to and allows in vivo detection of right-and left-sided thrombotic vegetations in experimental endocarditis. Superposition of autoradiography and corresponding histological section showed that, as in the aseptic mural thrombus in abdominal aortic aneurysms, 22 annexin V predominantly binds to the most luminal layer of the vegetation, corresponding to the dynamic biologically active interface between the circulating blood components and the vegetation. Because the Silastic catheter used for right-sided endocarditis is silicone rubber, as human pacemaker leads, imaging of phlebothrombosis associated with the venous catheter path is also of interest in detecting the extent of the septic-thrombotic process.…”

“…20,21 In a recent study, we have shown the ability of 99m Tc-ANX to assess the luminal renewal activity of chronic aseptic mural thrombi in an experimental model of abdominal aortic aneurysm. 22 Because endocardial vegetations and secondary embolic events can be regarded as septic platelet-rich thrombi, we investigated the ability of 99m Tc-ANX to provide functional imaging of endocardial vegetations and their embolic consequences using the classic experimental model of induced infective endocarditis in animals. 23 This ability has been assessed in both left-and right-sided vegetations and in 2 species: the rabbit model, which is the canonical one, and the rat model, which is more suited to small-animal imaging devices, to immunohistochemistry analysis, and for further experimental therapeutic studies.…”

Postchemotherapy and Tumor-Selective Targeting with the La-Specific DAB4 Monoclonal Antibody Relates to Apoptotic Cell Clearance

“…Although radiolabeled Annexin V may represent a promising cell-death detection technology for therapy response monitoring (9,10), outstanding problems with tumor-tobackground ratio and optimal imaging times remain for product design and clinical development. Moreover, phosphatidylserine is broadly expressed in inflamed tissue, in atherosclerotic plaques, during thrombosis (11)(12)(13)(14), and in dead noncancerous cells, which all reduce the tumor specificity of Annexin V.…”