Background. Abdominal aortic aneurysm (AAA) is a focal aortic dilatation progressing towards rupture. Non-invasive AAA-associated cell proliferation biomarkers are not yet established. We investigated the feasibility of the cell proliferation radiotracer, fluorine-18fluorothymidine ([ 18 F]FLT) with positron emission tomography/computed tomography (PET/ CT) in a progressive pre-clinical AAA model (angiotensin II, AngII infusion).
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.
Abdominal aortic aneurysm (AAA) is a focal dilation of the aorta associated with high mortality through rupture. Most of our understanding of the biology that drives AAA progression originates from surgical samples acquired in cases of elective open repair. These markers, which include macrophage infiltration and angiogenesis, have led to the exploration of novel radiopharmaceuticals to study AAA in preclinical models and human patients. Current clinical practice to detect AAA involves ultrasound-based screening and surveillance. Although ultrasound is cheap and without radiation risk, aortic diameter does not predict the heterogenous growth of AAA between patients. Positron emission tomography takes advantage of novel radiolabeled markers of disease to track biological changes. In human trials, the role of 2-[ 18 F]-fluorodeoxyglucose in detecting aneurysm growth and outcome is still debated, whereas sodium [ 18 F]-fluoride (microcalcification) has been shown to predict AAA growth and clinical outcome. Murine studies have been used to assess the suitability of radiotracers detecting inflammation, angiogenesis, and proliferation. However, in the absence of human data, the clinical suitability and applicability of these tracers remain speculative. This review examines how markers of AAA change over time and the ability of positron emission tomography to track these changes and discusses the radiopharmaceuticals that could have an application in stratifying AAA subjects.
The porcine pancreatic elastase (PPE) model is a common preclinical model of abdominal aortic aneurysms (AAA). Some notable characteristics of this model include the low aortic rupture rate, non-progressive disease course, and infra-renal AAA formation. Enhanced [18F]fluorothymidine ([18F]FLT) uptake on positron emission tomography/computed tomography (PET/CT) has previously been reported in the angiotensin II-induced murine model of AAA. Here, we report our preliminary findings of investigating [18F]FLT uptake in the PPE murine model of AAA. [18F]FLT uptake was found to be substantially increased in the abdominal areas recovering from the surgery, whilst it was not found to be significantly increased within the PPE-induced AAA, as confirmed using in vivo PET/CT and ex vivo whole-organ gamma counting (PPE, n = 7; controls, n = 3). This finding suggests that the [18F]FLT may not be an appropriate radiotracer for this specific AAA model, and further studies with larger sample sizes are warranted to elucidate the pathobiology contributing to the reduced uptake of [18F]FLT in this model.
In this letter, we explore the potential role of radionuclide-based molecular imaging modalities, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in evaluating abdominal aortic aneurysms (AAA). We further discuss how the developments of promising radiotracers in combination with ultra-sensitive PET and SPECT scanners may enable the assessment of AAA formation and progression and consequently patient risk stratification and therapeutic interventions.AAA is an asymptomatic, irreversible, focal enlargement of the abdominal aorta proceeding to rupture and eventually resulting in patient death. Patients with earlystage AAA do not exhibit evident signs or symptoms; hence, AAA is typically diagnosed during incidental health assessments or through dedicated screening programmes, such as those implemented in the USA, the UK and Sweden. Although many studies are conducted to identify more reliable and informative risk factors of AAA rupture, aortic size is the only marker utilised in clinical practice, with elective repair offered to prevent rupture once an AAA enlarges to the intervention threshold of 5.5 cm. The aortic diameter is a straightforward and convenient parameter to extract using ultrasound scanning (USS) but may not consistently correlate with prognosis, as large AAA may remain intact, while small AAA may rupture. 1 Much of our knowledge of human AAA pathology stems from aortic tissue obtained during surgery (i.e., latestage disease); therefore, theories based on findings corresponding to these tissues may not accurately reflect earlystage disease pathology, when an effective pharmacological treatment may be offered. Indeed, one of the most significant barriers to overcoming late-stage detection of AAA is the ability to detect early-stage molecular mechanisms that precede physical disease manifestation. Patient management can be complicated to navigate based solely onThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
claudication due to femoropopliteal occlusive disease. The addition of SEP to PTA can reduce the rate of symptomatic restenosis and reintervention.Summary: This is a randomized controlled trial "follow-up" of three treatments for claudication (PAT, SEP, or combination therapy). Inclusion criteria for the original study were patients with unilateral claudication due to femoropopliteal artery occlusive disease amenable to both PTA and supervised exercise. Suitable patients were treated for 3 months with best medical treatment and if their symptoms were stable were asked if they would be in the trial. After informed consent, they were randomization to PTA or SEP. The primary outcome was treadmill maximum walking distance (MWD) and Physical Function (PF) domain of the SF-36 Quality of Life questionnaire tool at 12 months. Secondary outcomes were ankle to brachial systolic blood pressure index (ABI), intermittent claudication distance (ICD), and patient-reported walking distance (PRWD), SF-36 domains except PF, King's College VascuQoL, restenosis and reintervention rates. This study was a call back to all participating patients who could be found. A detailed history cross checked by electronic and clinical records helped to ensure maximal capture of past data. A fixed load treadmill test (10 degree incline at 2.5 km/h) for a maximum of 5 minutes was conducted. All baseline variables were captured including ABI, MWD, ICD, and PRWD. The ceiling for MWD for those completing the treadmill test was 215 meters and the ceiling for PRWD was 1600 meters. The SF-36 questionnaire as well as the King's College VascuQoL for disease specific and generic evaluations were completed. All patients had an arterial duplex imaging of both legs in detail to determine any old or new lesions. The primary and secondary outcomes reflected those of the original study and by an intention to treat methodology. Of 178 patients who were initially recruited to the trial, 139 were alive at the time of follow-up (PTA, 46; SEP, 47; PTA + SEP, 46) and assessments were completed for 111 patients. Mortality before long-term evaluation was 24.4%, about 5% per year. Median time to long-term follow-up was 5.2 years. Patient demographics were similar between groups with median age 75. Sixty-nine patients (62.2%) were symptomatic and 18 (16.2%) had experienced a major cardiovascular event since their last follow-up visit. QoL outcomes demonstrated no significant difference between treatment groups. There was no significant difference observed in the primary end points of treadmill MWD or QoL outcomes, nor in the secondary end points of restenosis rates or new ipsilateral or contralateral lesions on duplex imaging. Improvement was observed in the ABI in all groups. PTA and PTA + SEP groups had a significantly higher ABI than the SEP group. Patients in all groups had subsequent interventions (PTA, 14; SEP, 10; PTA + SEP, 6). The total number of subsequent interventions was higher after PTA (n ¼ 29) compared with SEP (n ¼ 17) and PTA + SEP (n ¼ 9) but failed to r...
In the pursuit of understanding the pathological alterations that underlie ischaemic injuries, such as vascular remodelling and reorganisation, there is a need for recognising the capabilities and limitations of in vivo imaging techniques. Thus, this review presents contemporary published research of imaging modalities that have been implemented to study postischaemic neurovascular changes in small animals. A comparison of the technical aspects of the various imaging tools is included to set the framework for identifying the most appropriate methods to observe postischaemic neurovascular remodelling. A systematic search of the PubMed® and Elsevier’s Scopus databases identified studies that were conducted between 2008 and 2018 to explore postischaemic neurovascular remodelling in small animal models. Thirty-five relevant in vivo imaging studies are included, of which most made use of magnetic resonance imaging or positron emission tomography, whilst various optical modalities were also utilised. Notably, there is an increasing trend of using multimodal imaging to exploit the most beneficial properties of each imaging technique to elucidate different aspects of neurovascular remodelling. Nevertheless, there is still scope for further utilising noninvasive imaging tools such as contrast agents or radiotracers, which will have the ability to monitor neurovascular changes particularly during restorative therapy. This will facilitate more successful utility of the clinical imaging techniques in the interpretation of neurovascular reorganisation over time.
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