Fabrication and characterization of UV-emitting nanoparticles as novel radiation sensitizers targeting hypoxic tumor cells.

Radiation therapy is one of the primary therapeutic techniques for treating cancer, administered to nearly two-thirds of all cancer patients. Although largely effective in killing cancer cells, radiation therapy, like other forms of cancer treatment, has difficulty dealing with hypoxic regions within solid tumors. The incomplete killing of cancer cells can lead to recurrence and relapse. The research presented here is investigating the enhancement of the efficacy of radiation therapy by using scintillating nanoparticles that emit UV photons. UV photons, with wavelengths between 230 nm and 280 nm, are able to inactivate cells due to their direct interaction with DNA, causing a variety of forms of damage. UV-emitting nanoparticles will enhance the treatment in two ways: first by generating UV photons in the immediate vicinity of cancer cells, leading to direct and oxygen-independent DNA damage, and second by down-converting the applied higher energy X-rays into softer X-rays and particles that are more efficiently absorbed in the targeted tumor region. The end result will be nanoparticles with a higher efficacy in the treatment of hypoxic cells in the tumor, filling an important, unmet clinical need. Our preliminary experiments show an increase in cell death using scintillating LuPO4:Pr nanoparticles over that achieved by the primary radiation alone. This work describes the fabrication of the nanoparticles, their physical characterization, and the spectroscopic characterization of the UV emission. The work also presents in vitro results that demonstrate an enhanced efficacy of cell killing with x-rays and a low unspecific toxicity of the nanoparticles.

Optical Properties of Anisotropic Polycrystalline Ce+3 activated LSO.

Polycrystalline cerium activated lutetium oxyorthosilicate (LSO:Ce) is highly desirable technique to make cost effective and highly reproducible radiation detectors for medical imaging. In this article methods to improve transparency in polycrystalline LSO:Ce were explored. Two commercially available powders of different particulate sizes (average particle size 30 and 1500 nm) were evaluated for producing dense LSO:Ce by pressure assisted densification routes, such as hot pressing and hot isostatic pressing. Consolidation of the powders at optimum conditions produced three polycrystalline ceramics with average grain sizes of 500 nm, 700 and 2000 nm. Microstructural evolution studies showed that for grain sizes larger than 1 µm, anisotropy in thermal expansion coefficient and elastic constants of LSO, resulted in residual stress at grain boundaries and triple points that led to intragranular microcracking. However, reducing the grain size below 1 µm effectively avoids microcracking, leading to more favorable optical properties. The optical scattering profiles generated by a Stover scatterometer, measured by a He-Ne laser of wavelength 633 nm, showed that by reducing the grain size from 2 µm to 500 nm, the in-line transmission increased by a factor of 103. Although these values were encouraging and showed that small changes in grain size could increase transmission by almost 3 orders of magnitude, even smaller grain sizes need to be achieved in order to get truly transparent material with high in-line transmission.

Effect of Microstructure on the Radioluminescence and Transparency of Ce-Doped Strontium Hafnate Ceramics.

In this paper we report on the fabrication and characterization of SrHfO(3):Ce ceramics. Powders were prepared by solid-state synthesis using metal oxides and carbonates. X-ray diffraction measurements showed that phase-pure SrHfO(3) is formed at 1200°C. Inductively coupled plasma spectroscopy confirmed the purity and composition of each batch. SrHfO(3) exhibits several phase changes in the solid, but this does not appear to be detrimental to the ceramics. Microprobe experiments showed uniform elemental grain composition, whereas aluminum added as charge compensation for trivalent cerium congregated at grain boundaries and triple points. Radioluminescence spectra revealed that the light yield decreases when the concentration of excess Sr increases. The decrease in the light yield may be related to the change of Ce(3+) into Ce(4+) ions. For stoichiometric SrHfO(3):Ce, the light yield is about four times that of bismuth germanate (BGO), the conventional benchmark, indicating great potential for many scintillator applications.

Suppression of Afterglow in Microcolumnar CsI:Tl by Codoping With Sm: Recent Advances.

Microcolumnar CsI:Tl remains a highly desirable sensor for digital X-ray imaging due to its superior spatial resolution, bright emission, high absorption efficiency, and ready availability. Despite such obvious advantages, two characteristic properties of CsI:Tl undermine their use in clinical and high speed imaging: a persistent afterglow in its scintillation decay, and a hysteresis effect that distorts the scintillation yield after exposure to high radiation doses.In our earlier work we have discovered that the addition of 0.05 to 0.5 mol percent of Sm(2+) to crystals of CsI:Tl suppresses their afterglow by a factor of up to 50, even when subjected to a very high exposure of 120 R. This additive also diminishes hysteresis by an order of magnitude, which is a major accomplishment. Consequent- ly, our work is now focused on developing codoped microcolumnar CsI:Tl, Sm films that can potentially combine excellent properties of the current state-of-the-art CsI:Tl films with the reduced afterglow and hysteresis observed in codoped crystals. While our earlier attempts in CsI:Tl, Sm film fabrication, reported at the previous IEEE meeting, demonstrated obvious advantages of the approach, the recent work has succeeded in producing films that show improvement by at least a factor of 7 in afterglow and 150% in brightness compared to the standard CsI:Tl films. We report these important results in this paper, along with other recent advances in film growth and new imaging results.

Nondestructive method for quantifying thallium dopant concentrations in CsI:Tl crystals.

We report a quantitative method for using X-ray fluorescence (XRF) to nondestructively measure the true content of Tl dopant in CsI:Tl scintillator crystals. The instrument is the handheld LeadTracer™, originally developed at RMD Instruments for measuring Pb concentration in electronic components. We describe both the measurement technique and specific findings on how changes in crystal size and growth parameters affect Tl concentration. This method is also applicable to numerous other activator ions important to scintillators, such as Ce(3+) and Eu(2+).