Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque

Bartlett, Benjamin; Ludewick, Herbert P.; Lee, Silvia; Verma, Shipra; Francis, Roslyn J.; Dwivedi, Girish

doi:10.3390/cells10102573

Cited by 14 publications

(28 citation statements)

References 98 publications

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“…By contrast, the SEM images of the aorta (Figure 5d–f) show a singular solid plaque with a slab-like appearance. This is much more typical of more advanced disease and cardiac calcification, likely to be HAp, which forms as the plaque stabilises and becomes less prone to rupture [42, 76]. Both tracers showed increased uptake to a similar degree in this calcification in the aorta, but [ 18 F]NaF was more evident from images due to the different spatial resolutions of the radionuclides as previously discussed.…”

Section: Resultsmentioning

confidence: 82%

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

Keeling

Baark

Katsamenis

et al. 2022

Preprint

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Radiolabelled bisphosphonates (BPs) and [18F]NaF (18F-fluoride) are the two types of radiotracers available to image calcium mineralin vivo(e.g. bone), yet only [18F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using the highly sensitive nuclear imaging technique positron emission tomography (PET). These two radiotracers bind calcium mineral deposits via different mechanisms, with BPs chelating to calcium ions and thus being non-selective, and [18F]NaF being selective for hydroxyapatite (HAp) which is the main component of bone mineral. Taking into account that the composition of EC has been reported to include a diverse range of non-HAp calcium minerals, we hypothesised that BPs may be more sensitive for imaging EC due to their ability to bind to both HAp and non-HAp deposits. To test this hypothesis, we report a comparison between the68Ga-labelled BP tracer [68Ga]Ga-THP-Pam and [18F]NaF for PET imaging in a rat model of EC that develops macro- and microcalcifications in several organs. The presence of macrocalcifications was identified using preclinical computed tomography (CT) and microcalcifications were identified using μCT-based 3D X-ray histology (XRH) on isolated organs ex vivo. The morphological and mineral analysis of individual calcified deposits was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The PET imaging and ex vivo analysis results demonstrated that while both radiotracers behave similarly for bone imaging, the BP-based radiotracer [68Ga]Ga-THP-Pam was able to detect EC more sensitively in several organs in which the mineral composition departs from that of HAp. We conclude that BP-based PET radiotracers such as [68Ga]Ga-THP-Pam have a particular advantage for the sensitive imaging and early detection of EC by being able to detect a wider array of relevant calcium minerals in vivo than [18F]NaF, and should be evaluated clinically for this purpose.

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Section: Resultsmentioning

confidence: 82%

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

Keeling

Baark

Katsamenis

et al. 2022

Preprint

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“…Mice were fasted (water available) overnight prior to imaging. The mice were warmed for 30 min at ~ 30 °C and isoflurane anaesthesia was administered prior to intravenous (IV) injection of ~ 20 MBq of fluorodeoxyglucose (FDG) in a volume less than 200 μl 41 . Mice were kept warm during the uptake phase of 60 min under anaesthesia before cervical dislocation and part body PET-computed tomography (CT) scan on the BioPET/CT 105 camera (NSW, Australia) with a spatial resolution of 1.02 mm 41 .…”

Section: Methodsmentioning

confidence: 99%

“…The mice were warmed for 30 min at ~ 30 °C and isoflurane anaesthesia was administered prior to intravenous (IV) injection of ~ 20 MBq of fluorodeoxyglucose (FDG) in a volume less than 200 μl 41 . Mice were kept warm during the uptake phase of 60 min under anaesthesia before cervical dislocation and part body PET-computed tomography (CT) scan on the BioPET/CT 105 camera (NSW, Australia) with a spatial resolution of 1.02 mm 41 . InVivoScope software (Bioscan Inc.) and Syngio.via software (Siemens Healthineers, Australia) was used for image capture and analysis, respectively.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular changes after pneumonia in a dual disease mouse model

Bartlett

Ludewick

Verma

et al. 2022

Sci Rep

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Residual inflammation in cardiovascular organs is thought to be one of the catalysts for the increased risk of cardiovascular complications seen following pneumonia. To test this hypothesis, we investigated changes in plaque characteristics and inflammatory features in ApoE−/− mouse aorta and heart following pneumonia. Male ApoE−/− mice were fed a high fat diet for 8 weeks before intranasal inoculation with either Streptococcus pneumoniae serotype 4 (test group) or phosphate buffered saline (control group). Mice were sacrificed at 2-, 7- and 28-days post-challenge. Changes in plaque burden and characteristics in aortic root and thoracic aorta were characterized by Oil red O and Trichrome stains. Inflammatory changes were investigated by FDG-PET imaging and immunofluorescence staining. We found TIGR4-infected mice present with increased plaque presence in the aortic root and thoracic aorta at 2- and 28-days post-inoculation, respectively. Aortic wall remodelling was also more pronounced in mice challenged with pneumococci at 28 days post-inoculation. Aortic root plaques of infected mice had reduced collagen and smooth muscle cells, consistent with an unstable plaque phenotype. Pneumonia alters plaque burden, plaque characteristics, and aortic wall remodelling in ApoE−/− mice. These effects caused by Streptococcus pneumoniae TIGR4, may contribute to the increased risk of cardiovascular complications seen in survivors of this infection.

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“…Both tracers correlate negatively with plaque calcification [ 79 ]. This may be explained by the fact that not only macrophages, but other cells (like T-cells and smooth muscle cells), involved in the atherosclerotic process are presenting chemokine receptors on their surface [ 80 ].…”

Section: Evolution Of An Atherosclerotic Plaquementioning

confidence: 99%

Emerging Nuclear Medicine Imaging of Atherosclerotic Plaque Formation

et al. 2022

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Atherosclerosis is a chronic widespread cardiovascular disease and a major predisposing factor for cardiovascular events, among which there are myocardial infarction and ischemic stroke. Atherosclerotic plaque formation is a process that involves different mechanisms, of which inflammation is the most common. Plenty of radiopharmaceuticals were developed to elucidate the process of plaque formation at different stages, some of which were highly specific for atherosclerotic plaque. This review summarizes the current nuclear medicine imaging landscape of preclinical and small-scale clinical studies of these specific RPs, which are not as widespread as labeled FDG, sodium fluoride, and choline. These include oxidation-specific epitope imaging, macrophage, and other cell receptors visualization, neoangiogenesis, and macrophage death imaging. It is shown that specific radiopharmaceuticals have strength in pathophysiologically sound imaging of the atherosclerotic plaques at different stages, but this also may induce problems with the signal registration for low-volume plaques in the vascular wall.

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Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque

Cited by 14 publications

References 98 publications

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

Cardiovascular changes after pneumonia in a dual disease mouse model

Emerging Nuclear Medicine Imaging of Atherosclerotic Plaque Formation

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Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque

Cited by 14 publications

References 98 publications

68Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

68Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

Cardiovascular changes after pneumonia in a dual disease mouse model

Emerging Nuclear Medicine Imaging of Atherosclerotic Plaque Formation

Contact Info

Product

Resources

About

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

⁶⁸Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography