This paper is the first report describing how the concentrations of silicon and boron govern the cryogenic scintillation properties of n-type GaAs. It shows that valence band holes are promptly trapped on radiative centers and then combine radiatively with silicon donor band electrons at rates that increase with the density of free carriers. It also presents the range of silicon and boron concentrations needed for efficient light emission under X-ray excitation, which along with its low band gap and apparent absence of afterglow, make scintillating GaAs suitable for the detection of rare, low-energy electronic excitations from interacting dark matter particles. A total of 29 samples from four different suppliers were studied. Luminosities and timing responses were measured for the four principal emission bands centered at 860, 930, 1070, and 1335 nm, and for the total emissions. Excitation pulses of 40 kVp X-rays were provided by a light-excited X-ray tube driven by an ultra-fast laser. Scintillation emissions from 800 to 1350 nm were measured using an InGaAs photomultiplier. Within the concentration ranges of free carriers from 2 x 10(16)/cm(3) to 6 x 10(17)/cm(3) and boron from 1.5 x 10(18)/cm(3) to 6 x 10(18)/cm(3), nine samples have luminosities > 70 photons/keV and two have luminosities > 110 photons/keV. Other samples in that range have lower luminosities due to higher concentrations of non-radiative centers. The decay times decrease by typically a factor of ten with increasing free carrier concentrations from 10(17)/cm(3) to 2 x 10(18)/cm(3).

We describe a sol-gel synthetic method for the production of praseodymium-doped yttrium aluminum garnet (YAG) nanoparticles suitable for X-ray inducible photodynamic therapy (X-PDT). Our sol-gel based approach was optimized by varying temperature and time of calcination, resulting in nanoparticles that were smooth, spherical, and 50-200 nm in crystallite size. The powders were uniformly coated with a thin (10 nm) layer of silica to facilitate surface conjugation with functional moieties. Measurements of photon flux revealed that coated and uncoated powders emitted a similar photon emission spectrum in response to 50 keVp X-rays. We also determined that the presence of silica did not significantly reduce flux and the emission peak had a maximum at approximately 320 nm. Thus, these YAG:Pr powders are suitable candidates for future in vivo X-PDT studies. (C) 2018 Elsevier B.V. All rights reserved.

This paper is the first report of n-type GaAs as a cryogenic scintillation radiation detector for the detection of electron recoils from interacting dark matter (DM) particles in the poorly explored MeV/c2 mass range. Seven GaAs samples from two commercial suppliers and with different silicon and boron concentrations were studied for their low temperature optical and scintillation properties. All samples are n-type even at low temperatures and exhibit emission between silicon donors and boron acceptors that peaks at 1.33 eV (930 nm). The lowest excitation band peaks at 1.44 eV (860 nm), and the overlap between the emission and excitation bands is small. The X-ray excited luminosities range from 7 to 43 photons/keV. Thermally stimulated luminescence measurements show that n-type GaAs does not accumulate metastable radiative states that could cause afterglow. Further development and use with cryogenic photodetectors promises a remarkable combination of large target size, ultra-low backgrounds, and a sensitivity to electron recoils of a few eV that would be produced by DM particles as light as a few MeV/c2.

Background— There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[125I]iodorotenone (125I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of 123I-ZIROT in an intact large-animal model. Methods and Results— The 123I-ZIROT was administered during adenosine A2A agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, 123I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. 123I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At 123I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial 123I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or 99mTc-sestamibi from previous studies using a similar model. Furthermore, the 123I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). Conclusions— The ability of 123I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.

Epidermal growth factor receptors (EGFR), upregulated in many tumor types, have been a target for therapeutic development and molecular imaging. The objective of this study was to evaluate the distribution and metabolic characteristics of fluorine-18 labeled anilinoquinazolines as potential imaging agents for EGFR tyrosine kinase expression. Fluorine-18 labeled fluoronitrobenzenes were prepared by reaction of potassium cryptand [18F]fluoride with 1,2- and 1,4-dinitrobenzenes, and 3-nitro-N,N,N-trimethylanilinium triflate in 5 min. Decay-corrected radiochemical yields of [18F]fluoride incorporation into the nitro-aromatic compounds were 81 ± 2%, 44 ± 4% and 77 ± 5% (n = 3–5) for the 2-, 3- and 4-fluoro isomers, respectively. Sodium borohydride reduction to the corresponding [18F]fluoroanilines was achieved with greater than 80% conversion in 5 min. Coupling of [18F]fluoroaniline-hydrochlorides to 6,7-dimethoxy-4-chloro-quinazoline gave the corresponding 6,7-dimethoxy-4-(2-, 3- and 4-[18F]fluoroanilino)quinazolines in 31 ± 5%, 17 ± 2% and 55 ± 2% radiochemical yield, respectively, while coupling to the 6,7-diethoxy-4-chloro-quinazoline produced 6,7-diethoxy-4-(2-, 3- and 4-[18F]fluoroanilino)quinazolines in 19 ± 6%, 9 ± 3% and 36 ± 6% radiochemical yield, respectively, in 90 min to end of synthesis from [18F]fluoride. Biodistribution of 2- and 4-[18F]fluoroanilinoquinazolines was conducted in tumor-bearing mice (MDA-MB-435 and MDA-MB-468 xenografts). Low tumor uptake (<1% injected dose per gram (ID/g) of tissue up to 3 h postinjection of the radiotracers) was observed. High bone uptake (5–15% ID/g) was noted with the 4-[18F]fluoroanilinoquinazolines. The metabolic stabilities of radiolabeled quinazolines were further evaluated by incubation with human female cryopreserved isolated hepatocytes. Rapid degeneration of the 4-fluoro-substituted compounds to baseline polar metabolites was observed by radio-TLC, whereas, the 2- and 3-[18F]fluoroaniline derivatives were significantly more stable, up to 2 h, corroborating the in vivo biodistribution studies. para-Substituted [18F]fluoroanilines, a common structural motif in radiopharmaceuticals, are highly susceptible to metabolic degradation.

We report the scintillation luminosities, decay times, and emission wavelengths for 19 Ce3+ activated scintillators, 18 Eu2+ activated scintillators, and 4 self-activated scintillators. Of these, 18 have not been previously reported either as phosphors or scintillators. Their luminosities range from 40,000 to under 1000photons/MeV. While these scintillators may not have properties that make them top candidates for widespread use, their data will contribute to a deeper understanding of factors that limit scintillator performance.

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123 I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123 I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.

Single crystals of Ba0.96Eu0.04BrI (barium europium bromide iodide) were grown by the Bridgman technique. The title compound adopts the ordered PbCl2 structure [Braekken (1932). Z. Kristallogr. 83, 222-282]. All atoms occupy the fourfold special positions (4c, site symmetry m) of the space group Pnma with a statistical distribution of Ba and Eu. They lie on the mirror planes, perpendicular to the b axis at y = +-0.25. Each cation is coordinated by nine anions in a tricapped trigonal prismatic arrangement.

The goal of this work is to quantitatively compare fatty acid metabolism in the hearts of normal and spontaneously hypertensive rats (SHR) as a function of age, and thereby track physiological changes associated with the onset and progression of heart failure in the SHR model. We imposed a more-stringent negativity penalty for fully 4-D multiresolution B-spline SPECT image reconstruction, and applied this method to obtain weighted least-squares estimates of time-activity curves directly from projections for dynamic pinhole SPECT studies of 123I-labeled BMIPP fatty acid analog in the myocardium of both a normal rat and an SHR. Dynamic projection data were acquired for 60 min in 1-sec time frames with an angular step of 4 degrees per frame on a dual-head GE Millennium VG Hawkeye SPECT/CT scanner equipped with custom pinhole collimators. The time-varying spatial distribution of 123I-BMIPP was modeled with use of 4-D multiresolution B-splines that were piecewise constant in space and piecewise quadratic in time. The 4-D splines were organized on a 3-D spatial grid that provided sampling of 3.2 mm near the heart and 6.4 mm away from the heart. Temporal sampling intervals were 0–2.4, 2.4–9.4, 9.4–30, and 30–90 sec during the first gantry rotation. The use of nonuniform time sampling with B-splines that varied quadratically in time yielded smooth time-activity curves that captured the relatively fast rise and fall of 123I-BMIPP in the left ventricular blood pool, as well as the uptake and trapping of the radiotracer in the left ventricular myocardium. Compartmental modeling was then applied to the time-activity curves. This yielded quantitative metabolic rate estimates (Ki) of 0.60 min−1 and 0.22 min−1 in the normal and SHR hearts, respectively. The slower rate of fatty acid metabolism in the SHR is what one expects as the SHR heart switches to a reliance on gl- - ycolysis as the primary pathway for energy production during the development of heart failure. This fully 4-D image reconstruction method can also be applied to dynamic PET.

The scintillation properties of powders and single-crystals of BaFI doped with Eu2+ are presented. Single crystals were grown by the vertical Bridgman technique. Under optical and X-ray excitation, the samples exhibit a narrow Eu2+ 5d-4f transition emission centered at 405 nm. The scintillation light output is estimated to be 55,000 +/- 5,000 photons/MeV at 662 keV with 85% of the light decaying within 600 ns. An energy resolution of 8.5% full width at half maximum (FWHM) has been achieved using this scintillator for 662 keV excitation (Cs-137 source) at room temperature.

The scintillation properties of powders and single-crystals of BaFI doped with Eu 2+ are presented. Single crystals were grown by the vertical Bridgman technique. Under optical and X-ray excitation, the samples exhibit a narrow Eu 2+ 5d-4f transition emission centered at 405 nm. The scintillation light output is estimated to be 55,000±5,000 photons/MeV at 662 keV with 85% of the light decaying within 600 ns. An energy resolution of 8.5% full width at half maximum (FWHM) has been achieved using this scintillator for 662 keV excitation ( 137 Cs source) at room temperature.

Matrix metalloproteinase-14 (MT1-MMP or MMP-14) is a membrane-associated protease implicated in a variety of tissue remodeling processes and a molecular hallmark of select metastatic cancers. The ability to detect MMP-14 in vivo would be useful in studying its role in pathologic processes and may potentially serve as a guide for the development of targeted molecular therapies. Four MMP-14 specific probes containing a positively charged cell penetrating peptide (CPP) d-arginine octamer (r8) linked with a MMP-14 peptide substrate and attenuating sequences with glutamate (8e, 4e) or glutamate-glycine (4eg and 4egg) repeating units were modeled using an AMBER force field method. The probe with 4egg attenuating sequence exhibited the highest CPP/attenuator interaction, predicting minimized cellular uptake until cleaved. The in vitro MMP-14-mediated cleavage studies using the human recombinant MMP-14 catalytic domain revealed an enhanced cleavage rate that directly correlated with the linearity of the embedded peptide substrate sequence. Successful cleavage and uptake of a technetium-99m labeled version of the optimal probe was demonstrated in MMP-14 transfected human breast cancer cells. Two-fold reduction of cellular uptake was found in the presence of a broad spectrum MMP inhibitor. The combination of computational chemistry, parallel synthesis and biochemical screening, therefore, shows promise as a set of tools for developing new radiolabeled probes that are sensitive to protease activity.

We describe the design and operation of a high-throughput facility for synthesizing thousands of inorganic crystalline samples per year and evaluating them as potential scintillation detector materials. This facility includes a robotic dispenser, arrays of automated furnaces, a dual-beam X-ray generator for diffractometry and luminescence spectroscopy, a pulsed X-ray generator for time response measurements, computer-controlled sample changers, an optical spectrometer, and a network-accessible database management system that captures all synthesis and measurement data.

There is a well recognized need for a new generation of SPECT perfusion tracers with improved myocardial extraction over a wide flow range. 7′(Z)-[ 123 I]Iodorotenone (ZIROT) is a new myocardial perfusion imaging (MPI) agent with excellent myocardial uptake and favorable biodistribution. Our objective was to fully characterize the myocardial ZIROT extraction vs flow relationship during vasodilator stress in a large animal model. Accordingly, the adenosine A 2A receptor agonist ATL-146e was infused i.v. (0.3 μg/kg/min) in 5 anesthetized, open-chest dogs with critical LAD stenoses. When LCx flow was maximal, 111 MBq (3mCi) of ZIROT and microspheres were co-injected and the dogs were euthanized 5 min later. The LV was divided into 4 short axis slices for ex vivo imaging followed by gamma well counting of myocardial segments. At the time of ZIROT injection, transmural flow in the stenotic LAD zone was similar to baseline (0.90 ± 0.22 vs 0.87 ± 0.11 ml/min/g, respectively P = NS), whereas normal LCx zone flow increased significantly (3.25 ± 0.51 vs 1.00 ± 0.17 ml/min/g, P<0.05). As shown, myocardial ZIROT extraction tracked regional myocardial blood flow better than either 201 thallium or 99m Tc-sestamibi in our previous studies using a similar canine model. Furthermore, the ZIROT LAD/LCx activity ratios obtained by ex vivo imaging or gamma well counting (0.42 ± 0.08 and 0.45 ± 0.1 respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32 ± 0.09). The ability of ZIROT to more accurately track blood flow over a wide range makes it a very promising new MPI agent with potential for improved CAD detection and better quantitative estimation of the severity of flow impairment.