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) darginine 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.
Abstract-We describe the design and operation of a highthroughput 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 diffractometery 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.
The scintillation properties of BaBrI:Eu 2+ are reported. Crystals were produced by the vertical Bridgman technique in a sealed quartz ampoule. Excellent scintillation properties were measured. A light yield of 81,000 ± 3,000 photons per MeV (ph/MeV) of absorbed gamma-ray energy was measured. An energy resolution (FWHM over peak position) of 4.8 ± 0.5% was observed for the 662 keV full absorption peak. Pulsed x-ray luminescence measurements show two exponential decay components of 297 and 482 ns with a contribution to the total light output of 23 and 77%, respectively. Under X-ray and UV excitation, the emission corresponds to a broadband center at 413 nm. These intitial values make BaBrI:Eu 2+ one of the brightest and the fastest known Eu 2+ doped scintillators.Introduction Very few known scintillators have a good energy resolutions, which is essential for spectroscopic applications such as isotopic identification of nuclear materials. High luminosity and relatively high speed (less than 1 µs) are also highly desirable for these applications. Only 18 compounds are reported with an energy resolution of less than 6% [1]. Among those, only SrI 2 is activated by Eu 2+ . While activation with Eu 2+ yields scintillation light that is slower than that produced from Ce 3+ activation, it is still fast enough for many applications such as those related to national security. In this paper we present the scintillation properties of BaBrI:Eu 2+ . Barium mixed halides activated by Eu 2+ have been extensively studied as X-ray phosphors [2-4] but have not been investigated as scintillators.
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