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Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography.

ABSTRACT: Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights into in vivo atherosclerosis biology. Molecular imaging using positron emission tomography is unique in this field, with the potential to identify specific biological processes using either bespoke or re-purposed radiotracers. This review provides an overview of non-invasive vulnerable plaque detection and molecular imaging of coronary atherosclerosis.

SUBMITTER: Bing R

PROVIDER: S-EPMC7465858 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography.

Bing Rong R Loganath Krithika K Adamson Philip P Newby David D Moss Alastair A

The British journal of radiology 20191218 1113

Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights in ...[more]

PMID: 31821027

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Project description:Background and Purpose- The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18F-FDG or 18F-NaF uptake and recent or future cerebral ischemic events. Methods- A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen's d metric. Results- After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18F-FDG uptake than asymptomatic arteries (Cohen's d =0.492; CI=0.130-0.855; P=0.008) as well as significant heterogeneity (Cochran's Q =31.5; P=0.0005; I2=68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions- Recent ipsilateral cerebral ischemia may be associated with increased carotid 18F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18F-FDG or 18F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.

Project description:BackgroundImmunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software.Results68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3-100 µg in nude mice and approximately 1-100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3-10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109.Conclusion68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

Dataset Information

Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography.

Publications

Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography.

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