Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm

Gandhi, Richa; Cawthorne, Christopher; Craggs, Lucinda J L; Wright, John D.; Domarkas, Juozas; Ping, He; Koch-Paszkowski, Joanna; Shires, Michael; Scarsbrook, Andrew; Archibald, Stephen J.; Tsoumpas, Charalampos; Bailey, Marc A.

doi:10.1007/s12350-019-01946-y

Cited by 18 publications

(21 citation statements)

References 38 publications

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“…The suprarenal aortic volume was calculated in mm 3 (over the monitored distance of 12 mm) with Vevo Lab 3.1.1 software; images of ECG-gated kilohertz visualization were used to additionally determine the maximum diameter of the aorta (inner-to-inner wall) at maximal blood flow. 19 Independent measurements by 3 observers were averaged in volume and diameter calculations.…”

Section: Methodsmentioning

confidence: 99%

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms

Eilenberg

Zagrapan

Bleichert

et al. 2021

Translational Research

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Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P < 0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II -based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to

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Section: Methodsmentioning

confidence: 99%

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms

Eilenberg

Zagrapan

Bleichert

et al. 2021

Translational Research

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“…18 Using the angiotensin II-induced AAA murine model, Gandhi et al showed that there is increased [ 18 F]fluorothymidine ([ 18 F]FLT) uptake on day 14 post-aneurysm induction, but this uptake is significantly reduced on day 28. 19 These findings have important implications in supporting the idea of early-stage cellular remodeling that may drive disease progression, a notion that has been introduced and deliberated by several groups. [20][21][22] In the future, knowledge gained from these studies may facilitate early-stage risk stratification; however, further preclinical and clinical investigations are warranted to reinforce this theory.…”

Section: Preclinical Studiesmentioning

confidence: 83%

Prospect of positron emission tomography for abdominal aortic aneurysm risk stratification

Gandhi

Bell

Bailey

et al. 2021

Journal of Nuclear Cardiology

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Abdominal aortic aneurysm (AAA) disease is characterized by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions rely on aortic diameter measurements via abdominal ultrasound surveillance. However, AAA rupture can occur at small diameters or may never occur at large diameters, implying that anatomical size is not necessarily a sufficient indicator. Molecular imaging may help identify high-risk patients through AAA evaluation independent of aneurysm size, and there is the question of the potential role of positron emission tomography (PET) and emerging role of novel radiotracers for AAA. Therefore, this review summarizes PET studies conducted in the last 10 years and discusses the usefulness of PET radiotracers for AAA risk stratification. The most frequently reported radiotracer was [18F]fluorodeoxyglucose, indicating inflammatory activity and reflecting the biomechanical properties of AAA. Emerging radiotracers include [18F]-labeled sodium fluoride, a calcification marker, [64Cu]DOTA-ECL1i, an indicator of chemokine receptor type 2 expression, and [18F]fluorothymidine, a marker of cell proliferation. For novel radiotracers, preliminary trials in patients are warranted before their widespread clinical implementation. AAA rupture risk is challenging to evaluate; therefore, clinicians may benefit from PET-based risk assessment to guide patient management and surgical decisions.

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“…This study provides the first proof-of-concept data for PET-CT as a potential imaging assessment for AAA risk-stratification. A recent pre-clinical study using the AngII-infusion AAA model reported that the uptake of the cell proliferation radiotracer, Fluorine-18-fluorothymidine ((18F)FLT) is increased during the active growth phase of the AAA [ 102 ]. Addition of such novel radiotracer agents to PET-CT could enhance the ability to identify which AAAs require surgical repair.…”

Section: Use Of New Imaging Methods To Study Aaa Rupturementioning

confidence: 99%

Risk Factors and Mouse Models of Abdominal Aortic Aneurysm Rupture

Krishna

Morton

et al. 2020

IJMS

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Abdominal aortic aneurysm (AAA) rupture is an important cause of death in older adults. In clinical practice, the most established predictor of AAA rupture is maximum AAA diameter. Aortic diameter is commonly used to assess AAA severity in mouse models studies. AAA rupture occurs when the stress (force per unit area) on the aneurysm wall exceeds wall strength. Previous research suggests that aortic wall structure and strength, biomechanical forces on the aorta and cellular and proteolytic composition of the AAA wall influence the risk of AAA rupture. Mouse models offer an opportunity to study the association of these factors with AAA rupture in a way not currently possible in patients. Such studies could provide data to support the use of novel surrogate markers of AAA rupture in patients. In this review, the currently available mouse models of AAA and their relevance to the study of AAA rupture are discussed. The review highlights the limitations of mouse models and suggests novel approaches that could be incorporated in future experimental AAA studies to generate clinically relevant results.

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Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm

Cited by 18 publications

References 38 publications

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms

Prospect of positron emission tomography for abdominal aortic aneurysm risk stratification

Risk Factors and Mouse Models of Abdominal Aortic Aneurysm Rupture

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