Safe imaging agents able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran –ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI. The dextran-based probe could be detected via the contrast originating from dextran hydroxyl protons, thereby avoiding the need of chemical substitution for radioactive or metallic labelling. Because dextrans are currently used clinically, dextran-based contrast agents may help extend receptor-targeted imaging to clinical MRI.
Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively. To facilitate the targeted drug delivery of citicoline to ischemic regions, we prepared liposomes encapsulating citicoline (CDPC-lipo) and characterized the particle properties and CEST MRI properties. The in vivo CEST MRI detection of liposomal citicoline was then examined in a rat brain model of unilateral transient ischemia induced by a two-hour middle cerebral artery occlusion. The results showed that the delivery of CPDC-lipo to the brain ischemic areas could be monitored and quantified by CEST MRI. When administered intra-arterially, CDPC-lipo clearly demonstrated a detectable CEST MRI contrast at 2 ppm. CEST MRI revealed that liposomes preferentially accumulated in the areas of ischemia with a disrupted blood-brain-barrier. We furthermore used CEST MRI to detect the improvement in drug delivery using CDPC-lipo targeted against vascular cell adhesion molecule (VCAM)-1 in the same animal model. The MRI findings were validated using fluorescence microscopy. Hence, liposomal citicoline represents a prototype theranostic system, where the therapeutic agent can be detected directly by CEST MRI in a label-free fashion.
Although all dipteran species have ovaries of the same meroistic-polytrophic type, the structure of individual ovarian follicles (egg chambers) as well as the course of oogenesis in major dipteran taxa are highly diversified and often significantly different from the widely known Drosophila model. In this report we present results of the morphological studies of the ovary structure in the representatives of three families of lower brachycerans (Orthorrhapha) and compare them with the present knowledge of the processes that lead to the formation of a mature egg cell in the model dipteran, the cyclorrhaphan fruit fly, Drosophila melanogaster. The most conspicuous and developmentally significant differences between Drosophila and lower brachycerans were found in the events that accompany the differentiation and diversification of somatic follicular cells. Our observations indicate that the directed migrations of some follicular cells within the egg chamber and the ability of border cells to invade the nurse cell compartment can be considered as evolutionary novelties that evolved in the ancestors of higher brachycerans.
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