CARDIOVASCULAR RADIOLOGY / ORIGINAL PAPER
 
KEYWORDS
TOPICS
ABSTRACT
Purpose:
Monocyte chemoattractant protein-1 (MCP-1/CCL2) plays a key role for infiltration of monocytes/macrophages and studies have demonstrated that the MCP-1/C-C chemokine receptor 2 (CCR2) axis might be involved in the pathogenesis and progression of abdominal aortic aneurysms (AAA). Molecular imaging has shown potential for human clinical research studies. We evaluated the expression of CCR2 in patients with small AAA using single-photon emission computed tomography (SPECT) with the technetium-99m-6-hydrazinylnicotinoyl-C-C-chemokine receptor-2 ligand (99mTc-HYNIC-CCR2-L).

Material and methods:
A pilot study was performed to evaluate patients with small asymptomatic AAA. The equipment used was a Symbia T2 (Siemens, Germany), with radiolabeled 99mTc-HYNIC-CCR2-L. The SPECT uptake and activity were assessed and counted based on the region of interest (ROI), with nonparametric statistics being employed to compare the aneurysms site, left ventricle (Control 1) and regions with a nondiseased aorta (Control 2).

Results:
The three patients were male (100%) (mean age 81 years, and mean AAA maximum diameter of 40 mm, SD 3 mm). All patients tolerated the studies well. Images were obtained at one, two and four hours. The ROI mean value of the aneurysm site was 37,783 (SD 11,890), compared to the left ventricle (Control 1) 16,779 (SD 4397) (p-value = 0.0001); ROI for the nondiseased aortic region (Control 2) was significantly lower, 12,520 (SD 2141) (p-value = 0.0001).

Conclusions:
Significant differences of CCR2 expression SPECT were found in the AAA site compared to the left ventricle and nondiseased aortic segments. The introduction of well-designed longitudinal studies with nuclear imaging modalities may assist in the molecular characterization of aneurysmal and rupture prediction.

REFERENCES (28)
1.
Shen YH, LeMaire SA, Webb NR, Cassis LA, Daugherty A, Lu HS. Aortic aneurysms and dissections series. Arterioscler Thromb Vasc Biol 2020; 40: e37-e46. DOI: 10.1161/ATVBAHA.120.313991.
 
2.
Wanhainen A, Van Herzeele I, Bastos Goncalves F, Bellmunt Montoya S, Berard X, Boyle YR, et al. Editor’s Choice. European Society for Vascular Surgery (ESVS) 2024 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms. Eur J Vasc Endovasc Surg 2024; 67: 192-331.
 
3.
Salvador-González B, Martín-Baranera M, Borque-Ortega Á, Sáez-Sáez RM, de Albert-Delas Vigo M, Carreño-García E, et al. Prevalence of abdominal aortic aneurysm in men aged 65-74 years in a metropolitan area in North-East Spain. Eur J Vasc Endovasc Surg 2016; 52: 75-81.
 
4.
Hinojosa CA, Ibanez-Rodriguez JF, Serrato-Auld RC, Lozano-Corona R, Olivares-Cruz S, Lecuona-Huet NE, et al. Prevalence of abdominal aortic aneurysms in four different metropolitan areas in Mexico. Ann Vasc Surg 2022; 84: 218-224.
 
5.
Nordon IM, Hinchliffe RJ, Holt PJ, Loftus IM, Thompson MM. Review of current theories for abdominal aortic aneurysm pathoge­nesis. Vascular 2009; 17: 253-263.
 
6.
Bown MJ, Sweeting MJ, Brown LC, Powell JT, Thompson SG. Surveillance intervals for small abdominal aortic aneurysms: a meta-analysis. JAMA 2013; 309: 806-813.
 
7.
Eagleton MJ. Inflammation in abdominal aortic aneurysms: cellular infiltrate and cytokine profiles. Vascular 2012; 20: 278-283.
 
8.
Kurosawa K, Matsumura JS, Yamanouchi D. Current status of medical treatment for abdominal aortic aneurysm. Circ J 2013; 77: 2860-2866.
 
9.
Yoshimura T, Leonard EJ. Identification of high affinity receptors for human monocyte chemoattractant protein-1 on human monocytes. J Immunol 1990; 145: 292-297.
 
10.
Ajuebor MN, Flower RJ, Hannon R, Christie M, Bowers K, Verity A, et al. Endogenous monocyte chemoattractant protein-1 recruits monocytes in the zymosan peritonitis model. J Leukoc Biol 1998; 63: 108-116.
 
11.
Anaya-Ayala JE, Escamilla-Tilch M, Granados J, Hernandez-Dono S, Hernandez-Sotelo K, Lozano-Corona R, et al. Investigation of an immunogenetic profile in patients with abdominal aortic aneurysms and possible applications in screening and surveillance. Ann Vasc Surg 2020; 62: 57-62.
 
12.
Ferro-Flores G, Ocampo-García B, Cruz-Nova P, Luna-Gutiérrez M, Bravo-Villegas G, Azorín-Vega E, et al. 99mTc-labeled cyclic peptide targeting PD-L1 as a novel nuclear imaging probe. Pharmaceutics 2023; 15: 2662. DOI: 10.3390/pharmaceutics15122662.
 
13.
Elizondo-Benedetto S, Sastriques-Dunlop S, Detering L, Arif B, Heo GS, Sultan D, et al. Chemokine receptor 2 is a theranostic biomarker for abdominal aortic aneurysms. medRxiv [Preprint] 2023; 23298031. DOI: 10.1101/2023.11.06.23298031.
 
14.
English SJ, Sastriques SE, Detering L, Sultan D, Luehmann H, Arif B, et al. CCR2 positron emission tomography for the assessment of abdominal aortic aneurysm inflammation and rupture prediction. Circ Cardiovasc Imaging 2020; 13: e009889. DOI: 10.1161/CIRCIMAGING.119.009889.
 
15.
MA3RS Study Investigators. Aortic wall inflammation predicts abdominal aortic aneurysm expansion, rupture, and need for surgical repair. Circulation 2017; 136: 787-797.
 
16.
Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 2016; 44: 450-462.
 
17.
Kuznetsova T, Prange KHM, Glass CK, de Winther MPJ. Transcriptional and epigenetic regulation of macrophages in atherosclerosis. Nat Rev Cardiol 2020; 17: 216-228.
 
18.
Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am J Respir Cell Mol Biol 2015; 53: 676-688.
 
19.
Davis FM, Daugherty A, Lu HS. Updates of recent aortic aneurysm research. Arterioscler Thromb Vasc Biol 2019; 39: e83-e90. DOI: 10.1161/ATVBAHA.119.312000.
 
20.
Batra R, Suh MK, Carson JS, Dale MA, Meisinger TM, Fitzgerald M, et al. IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α) impact abdominal aortic aneurysm formation by differential effects on macrophage polarization. Arterioscler Thromb Vasc Biol 2018; 38: 457-463.
 
21.
Ishida Y, Kuninaka Y, Nosaka M, Kimura A, Taruya A, Furuta M, et al. Prevention of CaCl_2-induced aortic inflammation and subsequent aneurysm formation by the CCL3-CCR5 axis. Nat Commun 2020; 11: 5994. DOI: 10.1038/s41467-020-19763-0.
 
22.
Mejia-Cervantes J, Anaya-Ayala JE, Solano-Mendívil E, Gonzalez-Hernandez I, Aramburo JC, Medina-Velazquez LA, et al. Utility of multimodal molecular imaging in the diagnosis and decision-making in arterial diseases. Pol J Radiol 2024; 89: e6-e12. DOI: 10.5114/pjr.2024.134310.
 
23.
Anaya-Ayala JE, Verduzco-Vazquez AT, Medina LA, Marquina-Castillo BN, Aramburo JA, Bravo-Reyna C, et al. Analysis and interpretation of pathophysiologic mechanisms associated with the development and progression of thoracic aortic aneurysms through molecular imaging in murine models. EJVES Vascular Forum 2023; 58: 41-42.
 
24.
Chen W, Dilsizian V. PET assessment of vascular inflammation and atherosclerotic plaques: SUV or TBR? J Nucl Med 2015; 56: 503-504.
 
25.
Brangsch J, Reimann C, Collettini F, Buchert R, Botnar RM, Makowski MR. Molecular imaging of abdominal aortic aneurysms. Trends Mol Med 2017; 23: 150-164.
 
26.
Reeps C, Essler M, Pelisek J, Seidl S, Eckstein HH, Krause BJ. Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in posi­tron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms. J Vasc Surg 2008; 48: 417-424.
 
27.
Forsythe R, McBride O, Robson J, Graham C, Conlisk N, Hoskins P, et al. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study. NIHR Journals Library, Southampton (UK) 2018.
 
28.
Mathur A, Sharma AK, Murhekar VV, Mallia MB, Pawade S, Sarma HD, et al. Syntheses and biological evaluation of99mTc-HYNIC-fatty acid complexes for myocardial imaging. RSC Advances 2015; 5: 93374-93385.
 
Journals System - logo
Scroll to top