99mTc-Labeled 2-Arylbenzothiazoles: Aß Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography.

A series of 2-arylbenzothiazole derivatives conjugated with bis(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay-based screening was used to select seven rhenium complexes with potent binding affinity toward Aß1-42 aggregates (Ki < 50 nM) for 99mTc labeling and further evaluation. The 99mTc-labeled probes showed good affinity and specificity to Aß plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [99mTc]14b exhibited favorable brain pharmacokinetics in normal mice (2.11% ID/g at 2 min and 0.62% ID/g at 60 min). Ex vivo autoradiography revealed extensive labeling of Aß plaques by [99mTc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with 99mTc-labeled Aß probes. The semiquantitative data showed that [99mTc]14b penetrated the brains of rhesus monkeys. These results indicate that [99mTc]14b could be utilized as a SPECT imaging probe for Aß plaques.

(99m)Tc-labeled dibenzylideneacetone derivatives as potential SPECT probes for in vivo imaging of ß-amyloid plaque.

Four (99m)Tc-labeled dibenzylideneacetone derivatives and corresponding rhenium complexes were successfully synthesized and biologically evaluated as potential imaging probes for Aß plaques using SPECT. All rhenium complexes (5a-d) showed affinity for Aß(1-42) aggregates (Ki = 13.6-120.9 nM), and selectively stained the Aß plaques on brain sections of transgenic mice. Biodistribution in normal mice revealed that [(99m)Tc]5a-d exhibited moderate initial uptake (0.31%-0.49% ID/g at 2 min) and reasonable brain washout at 60 min post-injection. Although additional optimizations are still needed to facilitate it's penetration through BBB, the present results indicate that [(99m)Tc]5a may be a potential SPECT probe for imaging Aß plaques in Alzheimer's brains.

Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for ß-amyloid plaques.

A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as ß-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aß(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with (18)F ([(18)F]1a) for its high affinity (K(i)=28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82±0.51% ID/g at 2 min) into and moderate washout (2.77±0.31% ID/g at 60 min) from the brain. [(18)F]1a could be developed as a promising new PET imaging probe for Aß plaques although necessary modifications are still needed.

Novel cyclopentadienyl tricarbonyl complexes of (99m)Tc mimicking chalcone as potential single-photon emission computed tomography imaging probes for ß-amyloid plaques in brain.

Rhenium and technetium-99m cyclopentadienyl tricarbonyl complexes mimicking the chalcone structure were prepared. These complexes were proved to have affinity to ß-amyloid (Aß) in fluorescent staining on brain sections of Alzheimer's Disease (AD) patient and binding assay using Aß(1-42) aggregates, with K(i) values ranging from 899 to 108 nM as the extension of conjugated π system. In vitro autoradiograpy on sections of transgenic mouse brain confirmed the affinity of [(99m)Tc]5 (K(i) = 108 nM). In biodistribution, all compounds showed good initial uptakes into the brain and fast blood clearance, while the decreasing of initial brain uptakes correspond to increasing of conjugation length, from 4.10 ± 0.38% ID/g ([(99m)Tc]3) to 1.11 ± 0.34% ID/g ([(99m)Tc]5). These small technetium-99m complexes (<500 Da) designed by an integrated approach provide encouraging evidence that development of a promising (99m)Tc-labeled agent for imaging Aß plaques in the brain may be feasible.

¹8F-labeled 2-phenylquinoxaline derivatives as potential positron emission tomography probes for in vivo imaging of ß-amyloid plaques.

In continuation of our study on the 2-phenylquinoxaline scaffold as potential ß-amyloid imaging probes, two [(18)F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[(18)F]fluoroethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4a) and 2-(4-(2-(2-(2-[(18)F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4b) were prepared. Both of them displayed high binding affinity to Aß(1-42) aggregates (K(i) = 10.0 ± 1.4 nM for 4a, K(i) = 5.3 ± 3.2 nM for 4b). The specific and high binding of [(18)F]4a and [(18)F]4b to Aß plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [(18)F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [(18)F]4a may be a potential PET imaging agent for Aß plaques in the living human brain.

Synthesis and evaluation of novel ¹8F labeled 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives as ligands for positron emission tomography (PET) imaging of ß-amyloid plaques.

A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel ß-amyloid (Aß) imaging probes for PET. They displayed binding affinities for Aß(1-42) aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for (18)F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [(18)F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([(18)F]32) (K(i) = 8.0 ± 3.2 nM) displayed a brain(2min)/brain(60min) ratio of 4.66, which is highly desirable for Aß imaging agents. Target specific binding of [(18)F]32 to Aß plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [(18)F]32 is a promising Aß imaging agent for PET and merits further evaluation in human subjects.

Porous, platinum nanoparticle-adsorbed carbon nanotube yarns for efficient fiber solar cells.

Pt is a classical catalyst that has been extensively used in fuel cell and solar cell electrodes, owing to its high catalytic activity, good conductivity, and stability. In conventional fiber-shaped solar cells, solid Pt wires are usually adopted as the electrode material. Here, we report a Pt nanoparticle-adsorbed carbon nanotube yarn made by solution adsorption and yarn spinning processes, with uniformly dispersed Pt nanoparticles through the porous nanotube network. We have fabricated TiO(2)-based dye-sensitized fiber solar cells with a Pt-nanotube hybrid yarn as counter electrode and achieved a power conversion efficiency of 4.85% under standard illumination (AM1.5, 100 mW/cm(2)), comparable to the same type of fiber cells with a Pt wire electrode (4.23%). Adsorption of Pt nanoparticles within a porous nanotube yarn results in enhanced Pt-electrolyte interfacial area and significantly reduced charge-transfer resistance across the electrolyte interface, compared to a pure nanotube yarn or Pt wire. Our porous Pt-nanotube hybrid yarns have the potential to reduce the use of noble metals, lower the device weight, and improve the solar cell efficiency.

Synthesis and biological evaluation of novel technetium-99m labeled phenylbenzoxazole derivatives as potential imaging probes for ß-amyloid plaques in brain.

Two uncharged (99m)Tc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for ß-amyloid plaques. The (99m)Tc and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the ß-amyloid plaques on the sections of transgenic mouse, and showed high affinity for Aß((1-42)) aggregates (K(i)=11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [(99m)Tc]6 clearly labeled ß-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [(99m)Tc]6 displayed moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from the brain (0.25% ID/g at 60 min). The preliminary results indicate that the properties of [(99m)Tc]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier.

Synthesis and biological evaluation of 99mTc, Re-monoamine-monoamide conjugated to 2-(4-aminophenyl)benzothiazole as potential probes for beta-amyloid plaques in the brain.

The benzothiazole aniline (BTA) conjugated with monoamine-monoamide (MAMA) was synthesized and then labeled with (99m)Tc. Its corresponding rhenium analogue was synthesized, and the fluorescent staining was performed in brain sections of both Tg mouse and Alzheimer's disease (AD) patient. The fluorescent rhenium complex Re-MAMA-BTA selectively bound to the amyloid aggregates in the brain sections of both APP Tg mouse and AD patient. The analogous (99m)Tc-MAMA-BTA complex could enter the normal mouse brain with high initial uptake. These results are encouraging for further exploration of their derivatives as imaging agents for Abeta plaques in the brain.

Multiple exciton generation in colloidal silicon nanocrystals.

Multiple exciton generation (MEG) is a process whereby multiple electron-hole pairs, or excitons, are produced upon absorption of a single photon in semiconductor nanocrystals (NCs) and represents a promising route to increased solar conversion efficiencies in single-junction photovoltaic cells. We report for the first time MEG yields in colloidal Si NCs using ultrafast transient absorption spectroscopy. We find the threshold photon energy for MEG in 9.5 nm diameter Si NCs (effective band gap identical with Eg = 1.20 eV) to be 2.4 +/- 0.1Eg and find an exciton-production quantum yield of 2.6 +/- 0.2 excitons per absorbed photon at 3.4Eg. While MEG has been previously reported in direct-gap semiconductor NCs of PbSe, PbS, PbTe, CdSe, and InAs, this represents the first report of MEG within indirect-gap semiconductor NCs. Furthermore, MEG is found in relatively large Si NCs (diameter equal to about twice the Bohr radius) such that the confinement energy is not large enough to produce a large blue-shift of the band gap (only 80 meV), but the Coulomb interaction is sufficiently enhanced to produce efficient MEG. Our findings are of particular importance because Si dominates the photovoltaic solar cell industry, presents no problems regarding abundance and accessibility within the Earth's crust, and poses no significant environmental problems regarding toxicity.

Nanocrystalline TiO2 solar cells sensitized with InAs quantum dots.

We report nanocrystalline TiO2 solar cells sensitized with InAs quantum dots. InAs quantum dots of different sizes were synthesized and incorporated in solar cell devices. Efficient charge transfer from InAs quantum dots to TiO2 particles was achieved without deliberate modification of the quantum dot capping layer. A power conversion efficiency of about 1.7% under 5 mW/cm2 was achieved; this is relatively high for a nanocrystalline metal oxide solar cell sensitized with presynthesized quantum dots, but this efficiency could only be achieved at low light intensity. At one sun, the efficiency decreased to 0.3%. The devices are stable for at least weeks under room light in air.

PbTe colloidal nanocrystals: synthesis, characterization, and multiple exciton generation.

We report an alternative synthesis and the first optical characterization of colloidal PbTe nanocrystals (NCs). We have synthesized spherical PbTe NCs having a size distribution as low as 7%, ranging in diameter from 2.6 to 8.3 nm, with first exciton transitions tuned from 1009 to 2054 nm. The syntheses of colloidal cubic-like PbSe and PbTe NCs using a PbO "one-pot" approach are also reported. The photoluminescence quantum yield of PbTe spherical NCs was measured to be as high as 52 +/- 2%. We also report the first known observation of efficient multiple exciton generation (MEG) from single photons absorbed in PbTe NCs. Finally, we report calculated longitudinal and transverse Bohr radii for PbS, PbSe, and PbTe NCs to account for electronic band anisotropy. This is followed by a comparison of the differences in the electronic band structure and optical properties of these lead salts.

Highly efficient multiple exciton generation in colloidal PbSe and PbS quantum dots.

We report ultra-efficient multiple exciton generation (MEG) for single photon absorption in colloidal PbSe and PbS quantum dots (QDs). We employ transient absorption spectroscopy and present measurement data acquired for both intraband as well as interband probe energies. Quantum yields of 300% indicate the creation, on average, of three excitons per absorbed photon for PbSe QDs at photon energies that are four times the QD energy gap. Results indicate that the threshold photon energy for MEG in QDs is twice the lowest exciton absorption energy. We find that the biexciton effect, which shifts the transition energy for absorption of a second photon, influences the early time transient absorption data and may contribute to a modulation observed when probing near the lowest interband transition. We present experimental and theoretical values of the size-dependent interband transition energies for PbSe QDs. We present experimental and theoretical values of the size-dependent interband transition energies for PbSe QDs, and we also introduce a new model for MEG based on the coherent superposition of multiple excitonic states.

Absorption cross-section and related optical properties of colloidal InAs quantum dots.

We report the absorption cross-section of colloidal InAs quantum dots of mean radii from 1.6 to 3.45 nm. We find excellent agreement between the measured results and calculated values based on a model of small-particle light absorption. The absorption cross-section per dot is 6.2 x 10(-16)R(3) cm(2) at 2.76 eV and 3.15 x 10(-16)R(1.28) cm(2) at the first-exciton absorption peak, with the dot radius R in nm. We find that the per-quantum-dot particle oscillator strength of the first-exciton transition is constant for all sizes studied. The radiative lifetime of the first exciton calculated from the oscillator strength increases with dot size and ranges from 4 ns for the smallest dots to 14 ns for the largest ones.

Quenching of semiconductor quantum dot photoluminescence by a pi-conjugated polymer.

In this communication we discuss the possibility of hole transfer between a photoexcited semiconductor quantum dot and a pi-conjugated polymer. This charge-transfer event will be investigated (exploited) on the basis of its implication toward a solar energy conversion scheme. Experimentally, we show that the steady-state photoluminescence (PL) of a solution of InP quantum dots is quenched by the introduction of solvated poly(3-hexylthiophene). Time-resolved PL experiments on these solutions are also presented. It was observed that the PL transients did not significantly change upon the addition of the conductive polymer. These new results indicate that said PL quenching is static in nature. This suggests that in solution, the quantum dot and the polymer exhibit a strong intermolecular interaction. As the two species encounter each other through diffusion, the polymer quenches the quantum dot photoluminescence without altering the population's PL lifetime. This new evidence suggests that the polymer and the quantum dot form a relatively stable complex.