The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, ...that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols.
Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT.
Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.
These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.
•A large custom cryogen-free cryostat has been designed and built in order to operate the CUORE detector.•The CUORE cryostat has a 1 m3 experimental volume and is able to host a tonne-scale ...bolometric detector.•The CUORE cryostat guarantees a low noise and low radioactivity environment, needed to search for 0nbb.•The CUORE detector has been cooled down to 8.3 mK and steadily operated at 15 mK, proving the success of the cryostat.
The CUORE experiment is the world’s largest bolometric experiment. The detector consists of an array of 988 TeO2 crystals, for a total mass of 742 kg. CUORE is presently taking data at the Laboratori Nazionali del Gran Sasso, Italy, searching for the neutrinoless double beta decay of 130Te. A large custom cryogen-free cryostat allows reaching and maintaining a base temperature of ∼10 mK, required for the optimal operation of the detector. This apparatus has been designed in order to achieve a low noise environment, with minimal contribution to the radioactive background for the experiment. In this paper, we present an overview of the CUORE cryostat, together with a description of all its sub-systems, focusing on the solutions identified to satisfy the stringent requirements. We briefly illustrate the various phases of the cryostat commissioning and highlight the relevant steps and milestones achieved each time. Finally, we describe the successful cooldown of CUORE.
Next-generation experiments searching for rare events must satisfy increasingly stringent requirements on the bulk and surface radioactive contamination of their active and structural materials. The ...measurement of surface contamination is particularly challenging, as no existing technology is capable of separately measuring parts of the 232Th and 238U decay chains that are commonly found to be out of secular equilibrium. We will present the results obtained with a detector prototype consisting of 8 silicon wafers of 150 mm diameter instrumented as bolometers and operated in a low-background dilution refrigerator at the Gran Sasso Underground Laboratory of INFN, Italy. The prototype was characterized by a baseline energy resolution of few keV and a background <100 nBq/cm2 in the full range of α energies, obtained with simple procedures for cleaning of all employed materials and no specific measures to prevent recontamination. Such performance, together with the modularity of the detector design, demonstrate the possibility to realize an alpha detector capable of separately measuring all alpha emitters of the 232Th and 238U chains, possibly reaching a sensitivity of few nBq/cm2.
•Material screening.•Bolometric alpha detector.•Low-radioactivity measurements.
The CUORE Cryostat D’Addabbo, A.; Alduino, C.; Bersani, A. ...
Journal of low temperature physics,
12/2018, Letnik:
193, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
The Cryogenic Underground Observatory for Rare Events (CUORE) is a bolometric experiment for neutrinoless double-beta decay in
130
Te
search, currently taking data at the underground facility of ...Laboratori Nazionali del Gran Sasso (LNGS). The CUORE cryostat successfully cooled down a mass of about 1 ton at
∼
7
mK
, delivering a uniform and constant base temperature. This result marks a fundamental milestone in low-temperature detector techniques, opening the path for future ton-scale bolometric experiments searching for rare events. In this paper, we present the CUORE cryogenic infrastructure, briefly describing its critical subsystems.
We report a model that can be used to calculate superconducting transition temperature of a transition-edge sensor (TES), which is either a normal metal-superconductor-normal metal trilayer or a ...normal metal-superconductor bilayer. The model allows the T C estimation of a trilayer when the normal metals at the bottom and at the top are different. Furthermore, the model includes the spin flip time of the normal metals. We use the T C calculations from this model for selected Ir-based trilayers and bilayers to help understand potential designs of low T C TESs. A Au/Ir/Au trilayer can have a low T C because the superconducting order parameter is reduced with normal metals at both sides. On the other hand, an Ir/Pt bilayer can have a low T C because the much larger electron density of states of Pt reduces the superconducting order parameter more effectively. Moreover, the spin flip scattering of paramagnetic Pt also contributes to the T C reduction.
The Cryogenic Underground Observatory for Rare Events (CUORE) will search for the 0vββ decay in 130Te using a cryogenic array of TeO2 bolometers, operated at a base temperature of ~10mK. CUORE will ...consist of a closely packed array of 19 towers each containing 52 crystals, for a total mass of 741kg. The detector assembly is hosted in one of the largest cryostats ever constructed and will be cooled down to base temperature using a custom-built cryogen free dilution refrigerator. The CUORE cryostat along with the pulse tube based dilution refrigerator has been already commissioned at Laboratori Nazionali del Gran Sasso (LNGS) and a record base temperature, on a cubic meter scale, of ~6mK was achieved during one of the integration runs. We present the results from integration runs, characterizing the system and the cooling performance of the dilution refrigerator, effectively showcasing its stability at base temperature for the expected thermal load.
Broader clinical acceptance of photodynamic therapy is currently hindered by (a) poor depth efficacy, and (b) predisposition towards establishment of an angiogenic environment during the treatment. ...Improved depth efficacy is being sought by exploiting the NIR tissue transparency window and by photo-activation using two-photon absorption (2PA). Here, we use two-photon activation of PDT sensitizers, untargeted and targeted to SST2 receptors or EGF receptors, to achieve deep tissue treatment.
Human tumor lines, positive or negative for SST2r expression were used, as well as murine 3LL cells and bovine aortic endothelial cells. Expression of SST2 receptors on cancer cells and tumor vasculature was evaluated in vitro and frozen xenograft sections. PDT effects on tumor blood flow were followed using in vivo scanning after intravenous injection of FITC conjugated dextran 150K. Dependence of the PDT efficacy on the laser pulse duration was evaluated. Effectiveness of targeting to vascular SST2 receptors was compared to that of EGF receptors, or no targeting.
Tumor vasculature stained for SST2 receptors even in tumors from SST2 receptor negative cell lines, and SST2r targeted PDT led to tumor vascular shutdown. Stretching the pulse from ~120fs to ~3ps led to loss of the PDT efficacy especially at greater depth. PDT targeted to SST2 receptors was much more effective than untargeted PDT or PDT targeted to EGF receptors.
The use of octreotate to target SST2 receptors expressed on tumor vessels is an excellent approach to PDT with few recurrences and some long term cures.
•Targeting PDT to SST2 receptors is more efficient than to EGF receptors.•Using the same sensitizer, untargeted PDT was least effective.•SST2r targeting led to a number of cures whereas EGFr targeting did not.•SST2r targeting of PDT led to tumor vascular shutdown.•For two-photon activation, laser pulse parameters were critical for depth efficacy.
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