Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms

Abstract

Objective The aetiology and early pathophysiological mechanisms of aortic aneurysm formation are still unknown and challenging to study in vivo. Positron emission tomography (PET) is a potentially valuable instrument for non-invasive in vivo pathophysiological studies. No specific tracer to identify the pathophysiological process of aneurysmal dilatation is yet available, however. The aim of this study was to explore if different PET tracers could be useful to image aneurysmal disease.Methods and results Human aneurysmal aortic tissue, collected during elective resection of abdominal aortic aneurysm (AAA) of asymptomatic patients, was investigated in vitro by means of autoradiography with [68Ga]CRP-binder targeting C-reactive protein, [11C]DAA1106 targeting translocator protein (18 kDa), [11C]D-deprenyl with unknown target receptor, [11C]deuterium-L-deprenyl targeting astrocytes, [18F]fluciclatide targeting integrin αVβ3, [68Ga]IMP461 and bi-specific antibody TF2 052107 targeting carcinoembryonic antigen, [18F]F-metomidate targeting mitochondrial cytochrome P-450 species in the adrenal cortex, and [18F]vorozole targeting aromatase. Of the investigated tracers, only [18F]fluciclatide exhibited specific binding, whereas the other PET tracers failed to show specific uptake in the investigated tissue and are probably not useful for the intended purpose.Conclusion It seems likely that αVβ3 integrin expression in AAA can be visualized with PET and that the αVβ3 selective tracer, [18F]fluciclatide, may be suitable for in vivo molecular imaging of asymptomatic AAA. Additional evaluation of [18F]fluciclatide and αVβ3 integrin expression in AAA will be performed in vitro as well as in vivo.

Role of PET/CT in the Evaluation of Aortic Disease

“…Thus, because of the inconsistent results regarding FDG PET/CT, preclinical and clinical studies using various radiopharmaceuticals that can target different disease processes are currently underway to monitor the biological activity of aortic aneurysms. 68 Ga-DOTATATE, 35 11 C-PK11195, 36 18 F-cross-linked iron oxide nanoparticle 37 and 18 F-choline 38 39 40 can target macrophages, while 18 F-fluciclatide, 41 18 F-FPPRGD 42 and 64 Cu-NOTA-TRC105-Fab 43 can be used for neovascularization and angiogenesis in the process of aortic aneurysms. Another radiopharmaceutical targeting microcalcification, 44 18 F-Sodium fluoride (NaF), has critical clinical application in aortic aneurysms.…”

Monitoring the biological activity of abdominal aortic aneurysmsBeyond Ultrasound

“…Other potential PET tracers that may be useful in evaluating AAA disease do exist, 47 although research has so far been confined largely to preclinical autoradiography studies. 18 F-fluciclatide binds to integrins and has a high affinity for α v β 3 , which is expressed on endothelial cells, fibroblasts and inflammatory cells, and is known to be upregulated in angiogenesis.…”

“…One autoradiography study demonstrated that 18 F-fluciclatide detects areas of angiogenesis in AAA in vitro. 47 18F-FMISO (fluoromisonidazole) and 18 F-HX4 are radiotracers that selectively identify areas of hypoxia and have been used to localise high-risk carotid artery plaque reflecting increased macrophage activity. 48 Proteolytic degradation of collagen and elastin in the extracellular matrix is another key component in AAA formation.…”

Cross-Sectional Imaging to Evaluate the Risk of Rupture in Abdominal Aortic Aneurysms

“…On both PET and MRI, the development of contrast agents and tracers with organ or physiological process-specific affinity support the concept of molecular imaging. The future of molecular imaging lies in combining almost all contrast agents and radiotracers to specific ligands, such as membrane components of macrophages, platelets, oxidized low-density lipoproteins (LDL), and activated endothelia [ 80 81 ].…”