pinecone/core-2020-05-10-deduplication huggingface dataset:
Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide

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                  118587.pdf (author's version ) (Open Access)Integrin alphav beta3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine-glycine-aspartatic acid (RGD) peptide and integrin alphav beta3 , but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of (18)F. In this study, the dimeric RGD peptide, E-[c(RGDfK)]2, was conjugated with NODAGA and radiolabeled with (18)F in a simple one-pot process with a radiolabeling yield of 20%, the whole process lasting only 45 min. NODAGA-E-[c(RGDfK)]2 labeled with (18)F at a specific activity of 1.8 MBq nmol(-1) and a radiochemical purity of 100% could be achieved. The logP value of (18)F-labeled NODAGA-E-[c(RGDfK)]2 was -4.26 +/- 0.02. In biodistribution studies, (18)F-NODAGA-E-[c(RGDfK)]2 cleared rapidly from the blood with 0.03 +/- 0.01 percentage injected dose per gram (%ID g(-1)) in the blood at 2 h p.i., mainly via the kidneys, and showed good in vivo stability. Tumor uptake of (18)F-NODAGA-E-[c(RGDfK)]2 (3.44 +/- 0.20 %ID g(-1), 2 h p.i.) was significantly lower than that of reference compounds (68) Ga-labeled NODAGA-E-[c(RGDfK)]2 (6.26 +/- 0.76 %ID g(-1) ; p <0.001) and (111) In-labeled NODAGA-E-[c(RGDfK)]2 (4.99 +/- 0.64 %ID g(-1) ; p < 0.01). Co-injection of an excess of unlabeled NODAGA-E-[c(RGDfK)]2 along with (18)F-NODAGA-E-[c(RGDfK)]2 resulted in significantly reduced radioactivity concentrations in the tumor (0.85 +/- 0.13 %ID g(-1)). The alphav beta3 integrin-expressing SK-RC-52 tumor could be successfully visualized by microPET with (18)F-labeled NODAGA-E-[c(RGDfK)]2 . In conclusion, NODAGA-E-[c(RGDfK)]2 could be labeled rapidly with (18)F using a direct aqueous, one-pot method and it accumulated specifically in alphav beta3 integrin-expressing SK-RC-52 tumors, allowing for visualization by microPET
Sensitivity Enhancement of (Hyper-)CEST Image Series by Exploiting
  Redundancies in the Spectral Domain

CEST has proven to be a valuable technique for the detection of
hyperpolarized xenon-based functionalized contrast agents. Additional
information can be encoded in the spectral dimension, allowing the simultaneous
detection of multiple different biosensors. However, due to the low
concentration of dissolved xenon in biological tissue, the signal to noise
ratio (SNR) of Hyper-CEST data is still a critical issue. In this work, we
present two techniques aiming to increase SNR by exploiting the typically high
redundancy in spectral CEST image series: PCA-based post-processing and
sub-sampled acquisition with low-rank reconstruction. Each of them yields a
significant SNR enhancement, demonstrating the feasibility of the two
approaches. While the first method is directly applicable to proton CEST
experiments as well, the second one is particularly beneficial when dealing
with hyperpolarized nuclei, since it distributes the non-renewable initial
polarization more efficiently over the sampling points. The results obtained
are a further step towards the detection of xenon biosensors with spectral
Hyper-CEST imaging in vivo.Comment: To appear in Contrast Media and Molecular Imagin
Cell tracking using multimodal imaging

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                  125524.pdf (publisher's version ) (Open Access)In vivo imaging plays a key role in cell tracking, particularly for the optimization of cellular therapeutics. A recent trend is to use more than one imaging modality (multimodality imaging) for this purpose. There are several advantages to multimodal cell tracking, particularly the corroboration of data obtained using a new imaging agent or technique with an established one, and the ability to glean complementary information from a single experiment. In this review, we examine the different types of labels and imaging strategies used in the literature for multimodal cell tracking, and discuss the pros and cons of these approaches, with a focus on MRI. Despite many efforts and novel technologies, we still have to face situations where current imaging methods are simply not sensitive enough and new labeling strategies are hampered by the lack of approved reagents. Finally, we examine new in vitro and preclinical developments, which have the potential to tackle unresolved challenges in in vivo multimodal imaging. Copyright (c) 2013 John Wiley & Sons, Ltd
Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model

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                  137470.pdf (publisher's version ) (Open Access)The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using (18) F-Fluoromisonidazole (FMISO) and (18) F-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10 days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T2 * time increased significantly less in the bevacizumab group. FMISO uptake increased more over time in the control group. Vessel density significantly decreased in the bevacizumab-treated group. The Carbonic anhydrase 9 (CAIX) and glucose uptake transporter 1 (GLUT1) fractions were higher in bevacizumab-treated tumors. However, the hypoxic fraction showed no significant difference. Bevacizumab led to shorter T2 * times and higher GLUT1 and CAIX expression, suggesting an increase in hypoxia and a higher glycolytic rate. This could be a mechanism of resistance to bevacizumab. The increase in hypoxia, however, could not be demonstrated by pimonidazole/FMISO, possibly because distribution of these tracers is hampered by bevacizumab-induced effects on vascular permeability and perfusion. Copyright (c) 2014 John Wiley & Sons, Ltd
Targeting human prostate cancer with (111) In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts

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                  154086.pdf (publisher's version ) (Open Access)D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab')2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with (111) In-D2B IgG, (111) In-capromab pendetide, (111) In-D2B F(ab')2 and (111) In-D2B Fab fragments in mice with PSMA-expressing LNCaP and PSMA-negative PC3 tumors at several time points after injection. All (111) In-labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of (111) In-D2B IgG and (111) In-capromab pendetide at 168 h p.i. (94.8 +/- 19.2% injected dose per gram (ID/g) and 16.7 +/- 2.2% ID/g, respectively), whereas uptake of (111) In-D2B F(ab')2 and (111) In-D2B Fab fragments peaked at 24 h p.i. (12.1 +/- 3.0% ID/g and 15.1 +/- 2.9% ID/g, respectively). Maximum LNCaP tumor-to-blood ratios were 13.0 +/- 2.3 (168 h p.i.), 6.2 +/- 0.7 (24 h p.i.), 23.0 +/- 4.0 (24 h p.i.) and 4.5 +/- 0.6 (168 h p.i.) for (111) In-D2B IgG, (111) In-F(ab')2 , (111) In-Fab and (111) In-capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab')2 and Fab fragments for targeting PSMA-expressing prostate cancer xenografts. Copyright (c) 2014 John Wiley & Sons, Ltd
Therapy response monitoring of the early effects of a new BRAF inhibitor on melanoma xenograft in mice: evaluation of (18) F-FDG-PET and (18) F-FLT-PET

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                  154280.pdf (publisher's version ) (Open Access)Inhibition of the V600E mutated BRAF kinase gene (BRAF(V600E) ) is an important and effective approach to treating melanomas. A new specific small molecule inhibitor of BRAF(V600E) , PLX3603, showed potent melanoma growth-inhibiting characteristics in preclinical studies and is currently under clinical investigation. In this study we investigated the feasibility of (18) F-FDG and (18) F-FLT-PET to monitor the early effects of the BRAF(V600E) inhibitor in mice with melanoma xenografts. SCID/beige mice with subcutaneous (s.c.) A375 melanoma xenografts, expressing BRAF(V600E) , received the BRAF(V600E) inhibitor twice daily orally (0, 25, 50 and 75 mg/kg). At 1, 3 and 7 days after start of therapy, the uptake of (18) F-FDG and (18) F-FLT in the tumor and normal tissues was determined in ex vivo tissue samples. Serial (18) F-FDG and (18) F-FLT-PET scans were acquired of animals at 1 day before and 1, 3 and 7 days after start of treatment with 75 mg/kg BRAF(V600E) inhibitor. A dose-dependent decrease in (18) F-FDG uptake in the A375 tumors was observed by ex vivo biodistribution analysis. Administration of 75 mg/kg BRAF inhibitor for 1, 3 and 7 days resulted in a significantly decreased (18) F-FDG uptake in A375 tumors (41, 35 and 51%, respectively). (18) F-FLT uptake in the A375 tumors was low at baseline and no significant changes in (18) F-FLT uptake were observed at any of the doses administered. These effects were corroborated by serial in vivo (18) F-FDG and (18) F-FLT-PET imaging. These data demonstrate that (18) F-FDG-PET can be used as an imaging biomarker to noninvasively evaluate the early effects of PLX3603. Copyright (c) 2014 John Wiley & Sons, Ltd
Bioresponsive probes for molecular imaging: concepts and in vivo applications

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                  154651.pdf (publisher's version ) (Open Access)Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly two classes of bioresponsive imaging probes. The first class consists of probes that show direct activation of the imaging label (from "off" to "on" state) and have been applied in optical imaging and magnetic resonance imaging (MRI). The other class consists of probes that show specific retention of the imaging label at the site of target interaction and these probes have found application in all different imaging modalities, including photoacoustic imaging and nuclear imaging. In this review, we present a comprehensive overview of bioresponsive imaging probes in order to discuss the various molecular imaging strategies. The focus of the present article is the rationale behind the design of bioresponsive molecular imaging probes and their potential in vivo application for the detection of endogenous molecular targets in pathologies such as cancer and cardiovascular disease. Copyright (c) 2015 John Wiley & Sons, Ltd
Three-Dimensional Contrasted Visualization of Pancreas in Rats Using Clinical MRI and CT Scanners

The purpose of this work was to visualize the pancreas in post-mortem rats with local contrast medium infusion by three-dimensional (3D) magnetic resonance imaging (MRI) and computed tomography (CT) using clinical imagers. A total of 16 Sprague Dawley rats of about 300 g were used for the pancreas visualization. Following the baseline imaging, a mixed contrast medium dye called GadoIodo-EB containing optimized concentrations of Gd-DOTA, iomeprol and Evens blue was infused into the distally obstructed common bile duct (CBD) for post-contrast imaging with 3.0 T MRI and 128-slice CT scanners. Images were post-processed with the MeVisLab software package. MRI findings were co-registered with CT scans and validated with histomorphology, with relative contrast ratios quantified. Without contrast enhancement, the pancreas was indiscernible. After infusion of GadoIodo-EB solution, only the pancreatic region became outstandingly visible, as shown by 3D rendering MRI and CT and proven by colored dissection and histological examinations. The measured volume of the pancreas averaged 1.12 ± 0.04 cm(3) after standardization. Relative contrast ratios were 93.28 ± 34.61% and 26.45 ± 5.29% for MRI and CT respectively. We have developed a multifunctional contrast medium dye to help clearly visualize and delineate rat pancreas in situ using clinical MRI and CT scanners. The topographic landmarks thus created with 3D demonstration may help to provide guidelines for the next in vivo pancreatic MRI research in rodents. Copyright © 2015 John Wiley & Sons, Ltd.status: publishe
Hyperpolarized (6)Li as a probe for hemoglobin oxygenation level.

Hyperpolarization by dissolution dynamic nuclear polarization (DNP) is a versatile technique to dramatically enhance the nuclear magnetic resonance (NMR) signal intensity of insensitive long-T1 nuclear spins such as (6)Li. The (6)Li longitudinal relaxation of lithium ions in aqueous solutions strongly depends on the concentration of paramagnetic species, even if they are present in minute amounts. We herein demonstrate that blood oxygenation can be readily detected by taking advantage of the (6)Li signal enhancement provided by dissolution DNP, together with the more than 10% decrease in (6)Li longitudinal relaxation as a consequence of the presence of paramagnetic deoxyhemoglobin
PET of EGFR with (64) Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts

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                  171117.pdf (publisher's version ) (Open Access)Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to develop and characterize an EGFR-directed PET tracer, (64) Cu-cetuximab-F(ab')2 , to determine the systemic accessibility of EGFR. Mice with HNSCC xenografts, UT-SCC-8 (n = 6) or UT-SCC-45 (n = 6), were imaged 24 h post injection with (64) Cu-NODAGA-cetuximab-F(ab')2 using PET/CT. One mouse for each tumor model was co-injected with excess unlabeled cetuximab 3 days before radiotracer injection to determine non-EGFR-mediated uptake. Ex vivo biodistribution of the tracer was determined and tumors were analyzed by autoradiography and immunohistochemistry. The SUVmax of UT-SCC-8 tumors was higher than that of UT-SCC-45: 1.5 +/- 1.0 and 0.8 +/- 0.2 (p < 0.05), respectively. SUVmax after in vivo blocking of EGFR with cetuximab was 0.4. Immunohistochemistry showed that UT-SCC-8 had a significantly higher EGFR expression than UT-SCC-45: 0.50 +/- 0.19 versus 0.12 +/- 0.08 (p < 0.005), respectively. Autoradiography indicated that (64) Cu-cetuximab-F(ab')2 uptake correlated with EGFR expression in both tumors: r = 0.86 +/- 0.06 (UT-SCC-8) and 0.90 +/- 0.06 (UT-SCC-45). (64) Cu-cetuxmab-F(ab')2 is a promising PET tracer to determine expression of EGFR in vivo. Clinically, this tracer has the potential to be used to determine cetuximab targeting of tumors and possibly to non-invasively monitor the response to EGFR-inhibitor treatment. Copyright (c) 2015 John Wiley & Sons, Ltd
Localization, mechanism and reduction of renal retention of technetium-99m labeled epidermal growth factor receptor-specific nanobody in mice.

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                  96063.pdf (publisher's version ) (Open Access)BACKGROUND: Nanobodies are single-domain antigen binding fragments derived from functional heavy-chain antibodies elicited in Camelidae. They are powerful probes for radioimmunoimaging, but their renal uptake is relatively high. In this study we have evaluated the role of megalin on the renal uptake of anti-EGFR (99m)Tc-7C12 nanobody and the potency of gelofusine and/or lysine to reduce renal uptake of (99m)Tc-7C12. METHODS: First we compared the renal uptake of (99m)Tc-7C12 in megalin-deficient and megalin-wild-type mice using pinhole SPECT/microCT and ex vivo analysis. The effect of gelofusine and lysine administration on renal accumulation of (99m)Tc-7C12 was analyzed in CD-1 mice divided into lysine preload at 30 min before tracer injection (LysPreload), LysPreload + gelofusine coadministration (LysPreload + GeloCoad), lysine coadministration (LysCoad), gelofusine coadministration (GeloCoad) and LysCoad + GeloCoad. The combined effect of gelofusine and lysine on tumor uptake was tested in mice xenografts. RESULTS: Renal uptake of (99m)Tc-7C12 was 44.22 +/- 3.46% lower in megalin-deficient compared with megalin-wild-type mice. In CD-1 mice, lysine preload had no effect on the renal retention whereas coinjection of lysine or gelofusine with the tracer resulted in 25.12 +/- 2.99 and 36.22 +/- 3.07% reduction, respectively. The combined effect of gelofusine and lysine was the most effective, namely a reduction of renal retention of 45.24 +/- 2.09%. Gelofusine and lysine coadministration improved tumor uptake. CONCLUSION: Megalin contributes to the renal accumulation of (99m)Tc-7C12. Gelofusine and lysine coinjection with the tracer reduces the renal uptake while tumor uptake is improved. Although this methodology allows for optimization of imaging protocol using nanobodies, further improvements are needed before using these molecules for radionuclide therapy
Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas.

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                  109263.pdf (author's version ) (Open Access)Internalizing agonists are usually selected for peptide receptor targeting. There is increasing evidence that non-internalizing receptor antagonists can be used for this purpose. We investigated whether the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin(9-39) can be used for in vivo targeting of GLP-1R expressing tumours and compared the in vitro and in vivo characteristics with the GLP-1R agonists exendin-3 and exendin-4. The binding and internalization kinetics of labelled [Lys(40) (DTPA)]exendin-3, [Lys(40) (DTPA)]exendin-4 and [Lys(40) (DTPA)]exendin(9-39) were determined in vitro using INS-1 cells. The in vivo targeting properties of [Lys(40) ((111) In-DTPA)]exendin-3, [Lys(40) ((111) In-DTPA)]exendin-4 and [Lys(40) ((111) In-DTPA)]exendin(9-39) were examined in BALB/c nude mice with subcutaneous INS-1 tumours. (nat) In-labelled [Lys(40) (DTPA)]exendin-3, [Lys(40) (DTPA)]exendin-4 and [Lys(40) (DTPA)]exendin(9-39) exhibited similar IC(50) values (13.5, 14.4 and 13.4 n m, respectively) and bound to 26 x 10(3) , 41 x 10(3) and 37 x 10(3) receptors per cell, respectively. [Lys(40) ((111) In-DTPA)]exendin-3 and [Lys(40) ((111) In-DTPA)]exendin-4 showed rapid in vitro binding and internalization kinetics, whereas [Lys(40) ((111) In-DTPA)]exendin(9-39) showed lower binding and minimal internalization in vitro. In mice, high specific uptake of [Lys(40) ((111) In-DTPA)]exendin-3 [25.0 +/- 6.0% injected dose (ID) g(-1) ] in the tumour was observed at 0.5 h post-injection (p.i.) with similar uptake up to 4 h p.i. [Lys(40) ((111) In-DTPA)]exendin-4 showed higher tumour uptake at 1 and 4 h p.i. (40.8 +/- 7.0 and 41.9 +/- 7.2% ID g(-1), respectively). Remarkably, [Lys(40) ((111) In-DTPA)]exendin(9-39) showed only low specific uptake in the tumour at 0.5 h p.i. (3.2 +/- 0.7% ID g(-1)), rapidly decreasing over time. In conclusion, the GLP-1R agonists [Lys(40) (DTPA)]exendin-3 and [Lys(40) (DTPA)]exendin-4 labelled with (111) In could be useful for in vivo GLP-1R targeting, whereas [Lys(40) (DTPA)]exendin(9-39) is not suited for in vivo targeting of the GLP-1R
Magnetic Susceptibility: Solutions, Emulsions, and Cells

Differences in magnetic susceptibility between various compartments in
heterogeneous samples can introduce unanticipated complications to NMR spectra.
On the other hand, an understanding of these effects at the level of the
underlying physical principles has led to the development of several
experimental techniques that provide data on cellular function that are unique
to NMR spectroscopy. To illustrate some key features of susceptibility effects
we present, among a more general overview, results obtained with red blood
cells and a recently described model system involving diethyl phthalate in
water. This substance forms a relatively stable emulsion in water and yet it
has a significant solubility of 5 mmol/L at room temperature; thus, the NMR
spectrum has twice as many resonances as would be expected for a simple
solution. What determines the relative intensities of the two families of peaks
and can their frequencies be manipulated experimentally in a predictable way?
The theory used to interpret the NMR spectra from the model system and cells
was first developed in the context of electrostatics nearly a century ago, and
yet some of its underlying assumptions now warrant closer scrutiny. While this
insight is used in a practical way in this article, the accompanying article
deals with the mathematics and physics behind this new analysis.Comment: 15 pages, 9 figures, v2: updated to resemble the published versio
Magnetic Susceptibility: Further Insights into Macroscopic and
  Microscopic Fields and the Sphere of Lorentz

To make certain quantitative interpretations of spectra from NMR experiments
carried out on heterogeneous samples, such as cells and tissues, we must be
able to estimate the magnetic and electric fields experienced by the resonant
nuclei of atoms in the sample. Here, we analyze the relationships between these
fields and the fields obtained by solving the Maxwell equations that describe
the bulk properties of the materials present. This analysis separates the
contribution to these fields of the molecule in which the atom in question is
bonded, the "host" fields, from the contribution of all the other molecules in
the system, the "external" fields. We discuss the circumstances under which the
latter can be found by determining the macroscopic fields in the sample and
then removing the averaged contribution of the host molecule. We demonstrate
that the results produced by the, so-called, "sphere of Lorentz" construction
are of general validity in both static and time-varying cases. This analytic
construct, however, is not "mystical" and its justification rests not on any
sphericity in the system but on the local uniformity and isotropy, i.e.,
spherical symmetry, of the medium when averaged over random microscopic
configurations. This local averaging is precisely that which defines the
equations that describe the macroscopic fields. Hence, the external microscopic
fields, in a suitably averaged sense, can be estimated from the macroscopic
fields. We then discuss the calculation of the external fields and that of the
resonant nucleus in NMR experiments.Comment: 21 pages, 8 figures, v2: updated to resemble the published versio
Pulsed field gradient nuclear magnetic resonance as a tool for studying drug delivery systems

Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) is a versatile\ud
method for studying molecular transport and exchange in solution. Stejskal-Tanner diffusion plots can be used to distinguish between chemical species even in the absence of chemical shift or T1 resolution, provided that certain conditions are satisfied. This can be used advantageously in colloidal drug delivery systems containing two drug populations, free and bound, which often differ only by their diffusion coefficients. We discuss the conditions required for the resolution of the two pools in Stejskal-Tanner plots, as well as the effects of chemical exchange. We also present two practical examples of this analysis: surfactant micelles containing the general anesthetic propofol and lipid/water liquid crystalline mesophase vehicles (cubosomes)