Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T₁-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.

Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

Given the high sensitivity and specificity of sodium [¹⁸F]Fluoride (Na[¹⁸F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[¹⁸F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE^−/− mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[¹⁸F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[¹⁸F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[¹⁸F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[¹⁸F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity.

Despite recent medical advances, cardiovascular disease remains the leading cause of death worldwide. As (micro)-calcification is a hallmark of atherosclerosis, this review will elaborately discuss advantages of sodium fluoride positron emission tomography (PET) as a reliable cardiovascular imaging technique for identifying the early onset of vascular calcification (i.e. locking onto the target). We assess state-of-the-art meta-analysis and clinical studies of possible treatment options and evaluate the concept of vitamin K supplementation to preserve vascular health (i.e. loading the bullet). After a structured PubMed search, we identified ¹⁸F-sodium fluoride (¹⁸F-NaF) PET as the most suitable technique for detecting micro-calcification. Presenting the pros and cons of available treatments, vitamin K supplementation should be considered as a possible safe and cost-effective option to inhibit vascular (micro)-calcification. This review demonstrates need for more extensive research in the concept of vitamin K supplementation (i.e. loading the bullet) and recommends monitoring the effects on vascular calcification using ¹⁸F-NaF PET (i.e. locking onto the target).

By clearing GABA from the synaptic cleft, GABA transporters (GATs) play an essential role in inhibitory neurotransmission. Consequently, in vivo visualization of GATs can be a valuable diagnostic tool and biomarker for various psychiatric and neurological disorders. Not surprisingly, in recent years several research attempts to develop a radioligand have been conducted, but so far none have led to suitable radioligands that allow imaging of GATs. Here, we provide an overview of the radioligands that were developed with a focus on GAT1, since this is the most abundant transporter and most of the research concerns this GAT subtype. Initially, we focus on the field of GAT1 inhibitors, after which we discuss the development of GAT1 radioligands based on these inhibitors. We hypothesize that the radioligands developed so far have been unsuccessful due to the zwitterionic nature of their nipecotic acid moiety. To overcome this problem, the use of non-classical GAT inhibitors as basis for GAT1 radioligands or the use of carboxylic acid bioisosteres may be considered. As the latter structural modification has already been used in the field of GAT1 inhibitors, this option seems particularly viable and could lead to the development of more successful GAT1 radioligands in the future.