Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease

Abstract

Background Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET. Materials and methods The data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann–Whitney U test, Pearson correlation and Spearman correlation. Results 68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03–2.55] vs. 1.81 [1.56–1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). Conclusions 68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review

“…One additional study was found screening the references of the selected articles. Finally, 7 articles (198 patients) including data on the role of RGD-based PET agents in patients with cardiovascular diseases were included in the systematic review (16)(17)(18)(19)(20)(21)(22). The characteristics of the studies selected for the systematic review are presented in Tables 1-5.…”

“…Through the comprehensive computer literature search, 7 fulltext articles including data on the role of RGD-based PET agents in patients with cardiovascular diseases were selected (Table 1) (16)(17)(18)(19)(20)(21)(22). All the selected articles were published in the last 9 years.…”

“…The arterial segments assessed were internal and common carotid arteries, ascending aorta, aortic arch, descending aorta, Only one study included a binary visual analysis and found a positive signal in carotid plaques on PET using 68 Ga-NOTA-PRGD2 in only half of the patients (5 out of 10 patients) (17). Two studies focused on clinical correlates and found correlation with prior cardiovascular or cerebrovascular events as well as with history of hypercholesterolemia (19,21).…”

“…Morphological imaging was included in all studies. Two studies focused on CT plaque burden in large vessels and found correlation with CT calcium scoring and/or the indexed plaque volume (19,21). One study included further exploration using ultrasound and MR angiography and found a higher tracer accumulation in areas of the carotids with medium-or high-grade stenosis compared with areas with none/low-grade stenosis (17).…”

Advances in Radiopharmaceutical Sciences for Vascular Inflammation Imaging: Focus on Clinical Applications

“…For instance, the integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. αvβ3 integrin expression can be detected preclinically and clinically using peptides containing the RGD sequence derived PET probes such as the fluorinated and the gallium labeled [ 18 F]galacto-RGD [ 36 ] and [ 68 Ga]Ga-NOTA-RGD [ 37 ], respectively. Also, the clinical feasibility of imaging the fibroblast activation protein (FAP) in the human arterial vessel wall was recently demonstrated using the gallium-68-conjugated quinoline-based FAP inhibitor [ 68 Ga]Ga-DOTA-FAPI-04 [ 38 ].…”