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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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PET Imaging of the Neurotensin Targeting Peptide NOTA-NT-20.3 Using Cobalt-55, Copper-64 and Gallium-68

Introduction: Neurotensin receptor 1 (NTSR1) is an emerging target for imaging and therapy of many types of cancer. Nuclear imaging of NTSR1 allows for noninvasive assessment of the receptor levels of NTSR1 on the primary tumor, as well as potential metastases. This work focuses on a the neurotensin peptide analogue NT-20.3 conjugated to the chelator NOTA for radiolabeling for use in noninvasive positron emission tomography (PET). NOTA-NT-20.3 was radiolabeled with gallium-68, copper-64, and cobalt-55 to determine the effect that modification of the radiometal has on imaging and potential therapeutic properties of NOTA-NT-20.3. Methods: In vitro assays investigating cell uptake and subcellular localization of the radiolabeled peptides were performed using human colorectal adenocarcinoma HT29 cells. In vivo PET/CT imaging was used to determine the distribution and clearance of the peptide in mice bearing NTSR1 expressing HT29 tumors. Results: Cell uptake studies showed that the highest uptake was obtained with [ 55 Co] Co-NOTA-NT-20.3 (18.70 ± 1.30%ID/mg), followed by [ 64 Cu] Cu-NOTA-NT-20.3 (15.46 ± 0.91%ID/mg), and lastly [ 68 Ga] Ga-NOTA-NT-20.3 (10.94 ± 0.46%ID/mg) (p < 0.001). Subcellular distribution was similar across the three constructs, with the membranous fraction containing the highest amount of radioactivity. In vivo PET/CT imaging of the three constructs revealed similar distribution and tumor uptake at the 1 h imaging timepoint. Tumor uptake was receptor-specific and blockable by co-injection of non-radiolabeled NOTA-NT-20.3. SUV ratios of tumor to heart at the 24 h imaging timepoint show that [ 55 Co] Co-NOTA-NT-20.3 (20.28 ± 3.04) outperformed [ 64 Cu] Cu-NOTA-NT-20.3 (6.52 ± 1.97). In conclusion, our studies show that enhanced cell uptake and increasing tumor to blood ratios over time displayed the superiority of [ 55 Co] Co-NOTA-NT-20.3 over [ 68 Ga] Ga-NOTA-NT-20.3 and [ 64 Cu] Cu-NOTA-NT-20.3 for the targeting of NTSR1.

60 APPLIED LIFE SCIENCES↗

Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle

Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques. Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57/BL6 mice. To render iron oxide nanoparticles (IONP) specific for the extracellular MMP-2, the magnetic nanoparticle base material has been derivatized with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for the nuclear tracer 64 Cu labeling and the MMP-2-cleavable peptide modified with polyethylene glycol 2000, yielding a multi-modality reporter ( 64 Cu-NOTA-IONP@MMP2c-PEG2K, MMP2cNPs) for PET/MR imaging. Small animal PET imaging and biodistribution data revealed that MMP2cNPs exhibited remarkable plaque uptake (3.06 ± 0.87% ID/g and 1.83 ± 0.28% ID/g at 4 and 12 h, respectively). And MMP2cNPs were rapidly cleared from the contralateral normal carotid artery, resulting in excellent plaque-to-normal carotid artery contrasts. Furthermore, in vivo MRI showed a preferential accumulation of MMP2cNPs in atherosclerotic lesions compared with the non-cleavable reference compound, MMP2ncNPs. In addition, histological analyses revealed iron accumulations in the carotid atherosclerotic plaque, in colocalization with MMP-2 expression and macrophages. Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying the novel smart MMP2cNPs as a PET/MR hybrid imaging contrast agent for detection of MMP-2 in atherosclerotic plaque in vivo.

60 APPLIED LIFE SCIENCES↗

The Young Massive Star Cluster Westerlund 2 Observed with MUSE. III. A Cluster in Motion—The Complex Internal Dynamics

Analyzing the dynamical state of nearby young massive star clusters is essential for understanding star cluster formation and evolution during their earliest stages. In this work we analyze the stellar and gas kinematics of the young massive star cluster Westerlund 2 (Wd2) using data from the integral field unit Multi Unit Spectroscopic Explorer (MUSE) and complement them with proper motions from the Gaia DR2. The mean gas radial velocity of 15.9 km s{sup −1} agrees with the assumption that Wd2 is the result of a cloud–cloud collision. The gas motions show the expansion of the H ii region, driven by the radiation from the many OB stars in the cluster center. The velocity profile of the cluster member stars reveals an increasing velocity dispersion with decreasing stellar mass and that the low-mass stars show five distinct velocity groups. Based on their spatial correlation with the cluster’s two clumps, we concluded that this is the imprint of the initial cloud collapse that formed Wd2. A thorough analysis of the dynamical state of Wd2, which determines a dynamical mass range of M {sub dyn,Wd2} = (7.5 ± 1.9) × 10{sup 4} − (4.4 ± 1.1) × 10{sup 5} M {sub ⊙} and exceeds the photometric mass by at least a factor of two, leads to the conclusion that Wd2 is not massive enough to remain gravitationally bound. Additionally we also identify 22 runaway candidates with peculiar velocities between 30 and 546 km s{sup −1}.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Effect of low-stiffness closeout overwrap on rocket thrust-chamber life

Three rocket thrust chambers with copper liners and a thrust level of 20.9 kN were cyclically test fired to failure. Two of the liners were made from oxygen free, high conductivity (OFHC) copper and from annealed Amzirc. The milled coolant channels were closed out with a thin copper closeout over which a fiberglass composite was wrapped to provide hoop strength only. Experimental data are presented, along with the results of a preliminary analysis that was performed before fabrication to evaluate the life extending potential of a thin copper closeout with a fiberglass overwrap.

Kasper, H. J.↗

In-flight performance of the Faint Object Camera of the Hubble Space Telescope

An overview of the Faint Object Camera and its performance to date is presented. In particular, the detector's efficiency, the spatial uniformity of response, distortion characteristics, detector and sky background, detector linearity, spectrography, and operation are discussed. The effect of the severe spherical aberration of the telescope's primary mirror on the camera's point spread function is reviewed, as well as the impact it has on the camera's general performance. The scientific implications of the performance and the spherical aberration are outlined, with emphasis on possible remedies for spherical aberration, hardware remedies, and stellar population studies.

Greenfield, P.↗

The asymmetric wind of R127

We present optical, linear polarimetry in broad-band UBVRI filters plus narrow-band filters centered on the emission lines of H-alpha and the red forbidden N II and spectropolarimetry in the wavelength range from 4120 A to 6770 A of the luminous blue variable R127 in the LMC. Both observations display a decrease of the percentage polarization across the H-alpha emission line with respect to the continuum. We assume that H-alpha is recombination-line dominated and thus intrinsically unpolarized, and we use the continuum subtracted line polarization to estimate the interstellar foreground polarization. The resulting amount of intrinsic continuum polarization of R127 is very large, of order 1-1.5 percent, implying both the presence of copious free electrons and a considerable asphericity in their distribution. The two data sets, taken two months apart, display significant variations in the continuum polarization, which confirms that the stellar-wind properties of R127 are time-dependent in the maximum state. We discuss several possible wind geometries and present arguments favoring a clumpy, axisymmetric outflow.

Schulte-Ladbeck, R. E.↗

Hubble Space Telescope faint object camera instrument handbook (Post-COSTAR), version 5.0

The faint object camera (FOC) is a long-focal-ratio, photon-counting device capable of taking high-resolution two-dimensional images of the sky up to 14 by 14 arc seconds squared in size with pixel dimensions as small as 0.014 by 0.014 arc seconds squared in the 1150 to 6500 A wavelength range. Its performance approaches that of an ideal imaging system at low light levels. The FOC is the only instrument on board the Hubble Space Telescope (HST) to fully use the spatial resolution capabilities of the optical telescope assembly (OTA) and is one of the European Space Agency's contributions to the HST program.

Nota, A.↗

Geometry and physical conditions in the stellar wind of AG Carinae

AG Carinae is one of the prototypes of the class of Luminous Blue Variables (LBVs). Since 1990 the star has continuously brightened in its visual continuum. We report on a multi-instrument and -wavelength observing campaign to monitor the current activity phase of AG Car. Ground-based photometry, polarimetry, spectroscopy, and space-ultraviolet spectroscopy and spectropolarimetry have been obtained. From the variability of the polarization at ultraviolet and optical wavelengths we detect significant intrinsic polarization. P(sub int) greater than or equal to 0.5% is a large value for a hot, luminous star, suggesting departure from spherical symmetry in the wind of AG Car. The intrinsic polarization is variable on a timescale of 2 months or less. The measured ultraviolet polarization (intrinsic + interstellar) dropped to 0.5% in 1992 May and returned to 1% in 1992 July. The results are interpreted in terms of a variable outflow with a density enhancement in the equatorial plane. A similar model was suggested for the related object R127 in the Large Magellanic Cloud (LMC). This geometry is reminiscent of the large-scale morphology of the gas nebula and dust 'jet' surrounding AG Car. It is therefore likely that physical conditions close to the stellar surface are responsible for the geometry of the spatially resolved circumstellar material around AG Car. Despite the drastic change of the photospheric conditions, the mass-loss rate did not increase. We find no evidence for a positive correlation between wind density and stellar radius. This makes models that explain the radius increase by opacity effects in the outflow unlikely. The mechanism responsible for the temperature and radius variations is still unknown but most likely has its origin in subphotospheric regions.

Leitherer, Claus↗

Narrow band coronographic imaging of the bipolar nebula around the LBV R127

New high resolution narrow band coronographic images of the R127 nebula have been recently obtained. The nebula displays a bipolar morphology and is similar in appearance to the nebula around AG Carinae. The observations improve the values for the linear dimensions (1.9 x 2.2 pc) and yield an estimated nebular mass of 3.1 solar mass.

Clampin, Mark↗