975 resultados para Imaging diagnostic agents


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Advanced diagnostic techniques such as magnetic resonance imaging and computed tomography have become useful tools for confirmation of presumptive diagnosis of structural lesions in the brain such as encephalic neoplasms in small animal veterinary practice in Colombia, allowing an effective treatment planning that is more specific and less invasive for this type of pathology.

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Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

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Purpose: Dynamic near infrared fluorescence imaging of the urinary tract provides a promising way to diagnose ureteropelvic junction obstruction. Initial studies demonstrated the ability to visualize urine flow and peristalsis in great detail. We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic junction obstruction, renal involvement and the anatomical detail provided compared to conventional imaging modalities. Materials and Methods: Ten swine underwent partial or complete unilateral ureteral obstruction. Groups were survived for the short or the long term. Imaging was performed with mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic junction obstruction were developed for magnetic resonance urogram and near infrared imaging. Physicians and medical students graded ureteropelvic junction obstruction based on magnetic resonance urogram and near infrared imaging results. Results: Markers of vascular and urinary dynamics were quantitatively consistent among control renal units. The same markers were abnormal in obstructed renal units with significantly different times of renal phase peak, start of pelvic phase and start of renal uptake. Such parameters were consistent with those obtained with mercaptoacetyltriglycine diuretic renography. Near infrared imaging provided live imaging of urinary flow, which was helpful in identifying the area of obstruction for surgical planning. Physicians and medical students categorized the degree of obstruction appropriately for fluorescence imaging and magnetic resonance urogram. Conclusions: Near infrared imaging offers a feasible way to obtain live, dynamic images of urine flow and ureteral peristalsis. Qualitative and quantitative parameters were comparable to those of conventional imaging. Findings support fluorescence imaging as an accurate, easy to use method of diagnosing ureteropelvic junction obstruction.

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The aim of the current study was to investigate the exposure of captive wild felids to various infectious pathogens using serological and molecular methods. One hundred and fifty-nine neotropic felids and 51 exotic felids from 28 captive settings in Brazil were tested. While antibodies against Feline parvovirus and Feline coronavirus (FCoV), Feline calicivirus and Bartonella spp. were frequently detected by serologic tests, antibodies against Felid herpesvirus 1 or infection with hemotropic mycoplasmas were less prevalent. Serologic evidence of exposure to Ehrlichia spp., Feline immunodeficiency virus, and Feline leukemia virus (FeLV) was detected rarely, and infections with FeLV, Ehrlichia spp., and Cytauxzoon spp. were found infrequently. The detected Bartonella sequence was molecularly similar to B. koehlerae and B. henselae; for Cytauxzoon, the sequence resembled those from domestic cats. No Anaplasma phagocytophilum and Theileria spp. infections were detected. The positive test results varied significantly among different facilities and species. Additionally, FCoV seropositivity was more prevalent in captivity than in free-ranging populations. Results suggest that testing is appropriate prior to relocation of felids.

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Objectives: The objective of this study is to compare subjective image quality and diagnostic validity of cone-beam CT (CBCT) panoramic reformatting with digital panoramic radiographs. Materials and methods: Four dry human skulls and two formalin-fixed human heads were scanned using nine different CBCTs, one multi-slice CT (MSCT) and one standard digital panoramic device. Panoramic views were generated from CBCTs in four slice thicknesses. Seven observers scored image quality and visibility of 14 anatomical structures. Four observers repeated the observation after 4 weeks. Results: Digital panoramic radiographs showed significantly better visualization of anatomical structures except for the condyle. Statistical analysis of image quality showed that the 3D imaging modalities (CBCTs and MSCT) were 7.3 times more likely to receive poor scores than the 2D modality. Yet, image quality from NewTom VGi® and 3D Accuitomo 170® was almost equivalent to that of digital panoramic radiographs with respective odds ratio estimates of 1.2 and 1.6 at 95% Wald confidence limits. A substantial overall agreement amongst observers was found. Intra-observer agreement was moderate to substantial. Conclusions: While 2D-panoramic images are significantly better for subjective diagnosis, 2/3 of the 3D-reformatted panoramic images are moderate or good for diagnostic purposes. Clinical relevance: Panoramic reformattings from particular CBCTs are comparable to digital panoramic images concerning the overall image quality and visualization of anatomical structures. This clinically implies that a 3D-derived panoramic view can be generated for diagnosis with a recommended 20-mm slice thickness, if CBCT data is a priori available for other purposes.

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Although the diagnosis of Graves' orbitopathy is primarily made clinically based on laboratory tests indicative of thyroid dysfunction and autoimmunity, imaging studies, such as computed tomography, magnetic resonance imaging, ultrasound and color Doppler imaging, play an important role both in the diagnosis and follow-up after clinical or surgical treatment of the disease. Imaging studies can be used to evaluate morphological abnormalities of the orbital structures during the diagnostic workup when a differential diagnosis versus other orbital diseases is needed. Imaging may also be useful to distinguish the inflammatory early stage from the inactive stage of the disease. Finally, imaging studies can be of great help in identifying patients prone to develop dysthyroid optic neuropathy and therefore enabling the timely diagnosis and treatment of the condition, avoiding permanent visual loss. In this paper, we review the imaging modalities that aid in the diagnosis and management of Graves' orbitopathy, with special emphasis on the diagnosis of optic nerve dysfunction in this condition.

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The impact of plasma technologies is growing both in the academic and in the industrial fields. Nowadays, a great interest is focused in plasma applications in aeronautics and astronautics domains. Plasma actuators based on the Magneto-Hydro-Dynamic (MHD) and Electro- Hydro-Dynamic (EHD) interactions are potentially able to suitably modify the fluid-dynamics characteristics around a flying body without utilizing moving parts. This could lead to the control of an aircraft with negligible response time, more reliability and improvements of the performance. In order to study the aforementioned interactions, a series of experiments and a wide number of diagnostic techniques have been utilized. The EHD interaction, realized by means of a Dielectric Barrier Discharge (DBD) actuator, and its impact on the boundary layer have been evaluated by means of two different experiments. In the first one a three phase multi-electrode flat panel actuator is used. Different external flow velocities (from 1 to 20m/s) and different values of the supplied voltage and frequency have been considered. Moreover a change of the phase sequence has been done to verify the influence of the electric field existing between successive phases. Measurements of the induced speed had shown the effect of the supply voltage and the frequency, and the phase order in the momentum transfer phenomenon. Gains in velocity, inside the boundary layer, of about 5m/s have been obtained. Spectroscopic measurements allowed to determine the rotational and the vibrational temperature of the plasma which lie in the range of 320 ÷ 440°K and of 3000 ÷ 3900°K respectively. A deviation from thermodynamic equilibrium had been found. The second EHD experiment is realized on a single electrode pair DBD actuator driven by nano-pulses superimposed to a DC or an AC bias. This new supply system separates the plasma formation mechanism from the acceleration action on the fluid, leading to an higher degree of the control of the process. Both the voltage and the frequency of the nano-pulses and the amplitude and the waveform of the bias have been varied during the experiment. Plasma jets and vortex behavior had been observed by means of fast Schlieren imaging. This allowed a deeper understanding of the EHD interaction process. A velocity increase in the boundary layer of about 2m/s had been measured. Thrust measurements have been performed by means of a scales and compared with experimental data reported in the literature. For similar voltage amplitudes thrust larger than those of the literature, had been observed. Surface charge measurements led to realize a modified DBD actuator able to obtain similar performances when compared with that of other experiments. However in this case a DC bias replacing the AC bias had been used. MHD interaction experiments had been carried out in a hypersonic wind tunnel in argon with a flow of Mach 6. Before the MHD experiments a thermal, fluid-dynamic and plasma characterization of the hypersonic argon plasma flow have been done. The electron temperature and the electron number density had been determined by means of emission spectroscopy and microwave absorption measurements. A deviation from thermodynamic equilibrium had been observed. The electron number density showed to be frozen at the stagnation region condition in the expansion through the nozzle. MHD experiments have been performed using two axial symmetric test bodies. Similar magnetic configurations were used. Permanent magnets inserted into the test body allowed to generate inside the plasma azimuthal currents around the conical shape of the body. These Faraday currents are responsible of the MHD body force which acts against the flow. The MHD interaction process has been observed by means of fast imaging, pressure and electrical measurements. Images showed bright rings due to the Faraday currents heating and exciting the plasma particles. Pressure measurements showed increases of the pressure in the regions where the MHD interaction is large. The pressure is 10 to 15% larger than when the MHD interaction process is silent. Finally by means of electrostatic probes mounted flush on the test body lateral surface Hall fields of about 500V/m had been measured. These results have been used for the validation of a numerical MHD code.

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Noninvasive molecular-imaging technologies are playing a keyrole in drug discovery, development and delivery. Positron Emission Tomography (PET) is such a molecular imaging technology and a powerful tool for the observation of various diseases. However, it is limited by the availability of agents with high selectivity to the target and a physical half-life of the used positron emitting nuclide which matches the biological half-life of the observed process. For the long lasting enrichment of antibodies in tumor tissue few suitable isotopes for PET imaging are currently available. The element arsenic provides a range of isotopes, which could be used for diagnosis and also for endoradiotherapy. This work describes the development of radiochemical separation procedures to separate arsenic isotopes in no-carrier-added (nca) purity from reactor or cyclotron irradiated targets, the development and evaluation of a labeling chemistry to attach these separated arsenic isotopes to monoclonal antibodies, the in vitro and in vivo evaluation of antibodies labeled with radioactive arsenic isotopes and the molecular imaging using small animal PET.

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Neuronal circuits in the retina analyze images according to qualitative aspects such as color or motion, before the information is transmitted to higher visual areas of the brain. One example, studied for over the last four decades, is the detection of motion direction in ‘direction selective’ neurons. Recently, the starburst amacrine cell, one type of retinal interneuron, has emerged as an essential player in the computation of direction selectivity. In this study the mechanisms underlying the computation of direction selective calcium signals in starburst cell dendrites were investigated using whole-cell electrical recordings and two-photon calcium imaging. Analysis of the somatic electrical responses to visual stimulation and pharmacological agents indicated that the directional signal (i) is not computed presynaptically to starburst cells or by inhibitory network interactions. It is thus computed via a cell-intrinsic mechanism, which (ii) depends upon the differential, i.e. direction selective, activation of voltage-gated channels. Optically measuring dendritic calcium signals as a function of somatic voltage suggests (iii) a difference in resting membrane potential between the starburst cell’s soma and its distal dendrites. In conclusion, it is proposed that the mechanism underlying direction selectivity in starburst cell dendrites relies on intrinsic properties of the cell, particularly on the interaction of spatio-temporally structured synaptic inputs with voltage-gated channels, and their differential activation due to a somato-dendritic difference in membrane potential.

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The use of Magnetic Resonance Imaging (MRI) as a diagnostic tool is increasingly employing functional contrast agents to study or contrast entire mechanisms. Contrast agents in MRI can be classified in two categories. One type of contrast agents alters the NMR signal of the protons in its surrounding, e.g. lowers the T1 relaxation time. The other type enhances the Nuclear Magnetic Resonance (NMR) signal of specific nuclei. For hyperpolarized gases the NMR signal is improved up to several orders of magnitude. However, gases have a high diffusivity which strongly influences the NMR signal strength, hence the resolution and appearance of the images. The most interesting question in spatially resolved experiments is of course the achievable resolution and contrast by controlling the diffusivity of the gas. The influence of such diffusive processes scales with the diffusion coefficient, the strength of the magnetic field gradients and the timings used in the experiment. Diffusion may not only limit the MRI resolution, but also distort the line shape of MR images for samples, which contain boundaries or diffusion barriers within the sampled space. In addition, due to the large polarization in gaseous 3He and 129Xe, spin diffusion (different from particle diffusion) could play a role in MRI experiments. It is demonstrated that for low temperatures some corrections to the NMR measured diffusion coefficient have to be done, which depend on quantum exchange effects for indistinguishable particles. Physically, if these effects can not change the spin current, they can do it indirectly by modifying the velocity distribution of the different spin states separately, so that the subsequent collisions between atoms and therefore the diffusion coefficient can eventually be affected. A detailed study of the hyperpolarized gas diffusion coefficient is presented, demonstrating the absence of spin diffusion (different from particle diffusion) influence in MRI at clinical conditions. A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. The experimental measured diffusion agrees with theoretical simulations. Therefore, the molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this allows for images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion.

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Molecular imaging technologies as Positron Emission Tomography (PET) are playing a key role in drug discovery, development and delivery due to the possibility to quantify e.g. the binding potential in vivo, non-invasively and repetitively. In this context, it provides a significant advance in the understanding of many CNS disorders and conditions. The serotonergic receptor system is involved in a number of important physiological processes and diseases such as depression, schizophrenia, Alzheimer’s disease, sleep or sexual behaviour. Especially, the 5-HT2A and the 5-HT1A receptor subtypes are in the focus of fundamental and clinical research due to the fact that many psychotic drugs interact with these neuronal transmembrane receptors. This work describes the successful development, as well as in vitro and in vivo evaluation of 5-HT2A and 5-HT1A selective antagonistic PET-radiotracers. The major achievements obtained in this thesis are: 1. the development and in vitro evaluation of several 5-HT2A antagonistic compounds, namely MH.MZ (Ki = 9.0 nM), (R)-MH.MZ (Ki = 0.72 nM) and MA-1 (Ki = 3.0 nM). 2. the 18F-labeling procedure of these compounds and their optimization, whereby radiochemical yields > 35 % in high specific activities (> 15 GBq/µmol) could be observed. Synthesis time inclusive secondary synthon synthesis, the radioactive labeling procedure, separation and final formulation took no longer than 120 min and provided the tracer in high radiochemical purity. 3. the in vivo µPET evaluation of [18F]MH.MZ and (R)-[18F]MH.MZ resulting in promising imaging agents of the 5-HT2A receptor status; from which (R)-[18F]MH.MZ seems to be the most promising ligand. 4. the determination of the influence of P-gp on the brain biodistribution of [18F]MH.MZ showing a strong P-gp dependency but no regional alteration. 5. the four-step radiosynthesis and evaluation of [18F]MDL 100907 resulting in another high affine tracer, which is, however, limited due to its low radiochemical yield. 6. the development and evaluation of 3 novel possible 5-HT2A imaging agents combining structural elements of altanserin, MDL 100907 and SR 46349B demonstrating different binding modes of these compounds. 7. the development, the labeling and in vitro evaluation of the novel 5-HT1A antagonistic tracer [18F]AH1.MZ (Ki = 4.2 nM).

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In the last decades noble metal nanoparticles (NPs) arose as one of the most powerful tools for applications in nanomedicine field and cancer treatment. Glioblastoma multiforme (GBM), in particular, is one of the most aggressive malignant brain tumors that nowadays still presents a dramatic scenario concerning median survival. Gold nanorods (GNRs) and silver nanoparticles (AgNPs) could find applications such as diagnostic imaging, hyperthermia and glioblastoma therapy. During these three years, both GNRs and AgNPs were synthesized with the “salt reduction” method and, through a novel double phase transfer process, using specifically designed thiol-based ligands, lipophilic GNRs and AgNPs were obtained and separately entrapped into biocompatible and biodegradable PEG-based polymeric nanoparticles (PNPs) suitable for drug delivery within the body. Moreover, a synergistic effect of AgNPs with the Alisertib drug, were investigated thanks to the simultaneous entrapment of these two moieties into PNPs. In addition, Chlorotoxin (Cltx), a peptide that specifically recognize brain cancer cells, was conjugated onto the external surface of PNPs. The so-obtained novel nanosystems were evaluated for in vitro and in vivo applications against glioblastoma multiforme. In particular, for GNRs-PNPs, their safety, their suitability as optoacoustic contrast agents, their selective laser-induced cells death and finally, a high tumor retention were all demonstrated. Concerning AgNPs-PNPs, promising tumor toxicity and a strong synergistic effect with Alisertib was observed (IC50 10 nM), as well as good in vivo biodistribution, high tumor uptake and significative tumor reduction in tumor bearing mice. Finally, the two nanostructures were linked together, through an organic framework, exploiting the click chemistry azido-alkyne Huisgen cycloaddition, between two ligands previously attached to the NPs surface; this multifunctional complex nanosystem was successfully entrapped into PNPs with nanoparticles’ properties maintenance, obtaining in this way a powerful and promising tool for cancer fight and defeat.

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Environmental decay in porous masonry materials, such as brick and mortar, is a widespread problem concerning both new and historic masonry structures. The decay mechanisms are quite complex dependng upon several interconnected parameters and from the interaction with the specific micro-climate. Materials undergo aesthetical and substantial changes in character but while many studies have been carried out, the mechanical aspect has been largely understudied while it bears true importance from the structural viewpoint. A quantitative assessment of the masonry material degradation and how it affects the load-bearing capacity of masonry structures appears missing. The research work carried out, limiting the attention to brick masonry addresses this issue through an experimental laboratory approach via different integrated testing procedures, both non-destructive and mechanical, together with monitoring methods. Attention was focused on transport of moisture and salts and on the damaging effects caused by the crystallization of two different salts, sodium chloride and sodium sulphate. Many series of masonry specimens, very different in size and purposes were used to track the damage process since its beginning and to monitor its evolution over a number of years Athe same time suitable testing techniques, non-destructive, mini-invasive, analytical, of monitoring, were validated for these purposes. The specimens were exposed to different aggressive agents (in terms of type of salt, of brine concentration, of artificial vs. open-air natural ageing, …), tested by different means (qualitative vs. quantitative, non destructive vs. mechanical testing, punctual vs. wide areas, …), and had different size (1-, 2-, 3-header thick walls, full-scale walls vs. small size specimens, brick columns and triplets vs. small walls, masonry specimens vs. single units of brick and mortar prisms, …). Different advanced testing methods and novel monitoring techniques were applied in an integrated holistic approach, for quantitative assessment of masonry health state.

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This thesis work deals, principally, with the development of different chemical protocols ranging from environmental sustainability peptide synthesis to asymmetric synthesis of modified tryptophans to a series of straightforward procedures for constraining peptide backbones without the need for a pre-formed scaffold. Much efforts have been dedicated to the structural analysis in a biomimetic environment, fundamental for predicting the in vivo conformation of compounds, as well as for giving a rationale to the experimentally determined bioactivity. The conformational analyses in solution has been done mostly by NMR (2D gCosy, Roesy, VT, titration experiments, molecular dynamics, etc.), FT-IR and ECD spectroscopy. As a practical application, 3D rigid scaffolds have been employed for the synthesis of biological active compounds based on peptidomimetic and retro-mimetic structures. These mimics have been investigated for their potential as antiflammatory agents and actually the results obtained are very promising. Moreover, the synthesis of Amo ring permitted the development of an alternative high effective synthetic pathway for obtaining Linezolid antibiotic. The final section is, instead, dedicated to the construction of a new biosensor based on zeolite L SAMs functionalized with the integrin ligand c[RGDfK], that has showed high efficiency for the selective detection of tumor cells. Such kind of sensor could, in fact, enable the convenient, non-invasive detection and diagnosis of cancer in early stages, from a few drops of a patient's blood or other biological fluids. In conclusion, the researches described herein demonstrate that the peptidomimetic approach to 3D definite structures, allows unambiguous investigation of the structure-activity relationships, giving an access to a wide range bioactive compounds of pharmaceutical interest to use not only as potential drugs but also for diagnostic and theranostic applications.

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Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new 18F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed 18F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable 18F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for 18F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K⊂2.2.2]+/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved.rnThe promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were conducted. The synthesis of the folate-boron clusters was straightforward. At first, a linker molecule based on maleic acid was synthesized, which was coupled to the boron cluster via Michael Addition of a thiol and alkene and subsequently coupled to the targeting moiety using CuAAC. The new conjugates of folate and boron clusters led to a significant increase of boron concentration in the cell of about 5-times compared to currently used and approved boron pharmaceuticals. rnMoreover, azido-folate derivatives were coupled to macromolecular carrier systems (pHPMA), which showed an enhanced and specific accumulation at target sites (up to 2.5-times) during in vivo experiments. A specific blockade could be observed up to 30% indicating an efficient targeting effect. A new kind of nanoparticles consisting of a PDLLA core and p((HPMA)-b-LMA)) as surfactants were developed and successfully radiolabeled via 18F-click chemistry in good RCYs of 8±3%rnThe nanoparticles were obtained via the miniemulsion technique in combination with solvent evaporation. The 18F-labeled nanoparticles were applied to in vivo testing using a mouse model. PET imaging showed a “mixed” biodistribution of low molecular weight as well as high molecular weight systems, indicating a partial loss of the 18F-labeled surfactant.rnIn conclusion, the presented work successfully utilized the FR-targeting concept in both, the diagnostic field (PET imaging) and for therapeutic approaches (BNCT, drug delivery systems). As a result, the high potential of FR-targeting in oncological applications has been shown and was confirmed by small animal PET imaging.rn