silicon and Prostatic-Neoplasms

Proton therapy of prostate cancer (PCPT) was linked with increased levels of gastrointestinal toxicity in its early use compared to intensity-modulated radiation therapy (IMRT). The higher radiation dose to the rectum by proton beams is mainly due to anatomical variations. Here, we demonstrate an approach to monitor rectal radiation exposure in PCPT based on prompt gamma spectroscopy (PGS). Endorectal balloons (ERBs) are used to stabilize prostate movement during radiotherapy. These ERBs are usually filled with water. However, other water solutions containing elements with higher atomic numbers, such as silicon, may enable the use of PGS to monitor the radiation exposure of the rectum. Protons hitting silicon atoms emit prompt gamma rays with a specific energy of 1.78 MeV, which can be used to monitor whether the ERB is being hit. In a binary approach, we search the silicon energy peaks for every irradiated prostate region. We demonstrate this technique for both single-spot irradiation and real treatment plans. Real-time feedback based on the ERB being hit column-wise is feasible and would allow clinicians to decide whether to adapt or continue treatment. This technique may be extended to other cancer types and organs at risk, such as the oesophagus.

Topics: Balloon Enteroscopy; Gamma Rays; Humans; Male; Prostate; Prostatic Neoplasms; Proton Therapy; Radiation Injuries; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Rectum; Silicon; Spectrum Analysis

Information about the characteristics of measuring chips according to their storage conditions is of great importance for clinical diagnosis. In our present work, we have studied the capability of chips to detect nanowire biosensors when they are either freshly prepared or have been stored for either one or two years in a clean room. Potential to detect DNA oligonucleotides (oDNAs)-synthetic analogues of microRNAs (miRNAs) 198 and 429 that are associated with the development of prostate cancer (PCa)-in buffer solution was demonstrated using a nanowire biosensor based on silicon-on-insulator structures (SOI-NW biosensor). To provide biospecific detection, nanowire surfaces were sensitized with oligonucleotide probes (oDNA probes) complimentary to the known sequences of miRNA 183 and 484. In this study it is demonstrated that freshly prepared SOI-NW biosensor chips with n-type conductance and immobilized oDNA probes exhibit responses to the addition of complimentary oDNAs in buffer, leading to decreases in chips' conductance at a concentration of 3.3 × 10

Topics: Biomarkers, Tumor; Biosensing Techniques; Humans; Male; MicroRNAs; Nanowires; Nucleic Acids; Prostatic Neoplasms; Silicon

Gene silencing by RNA interference is a powerful technology with broad applications. However, this technology has been hampered by the instability of small interfering RNA (siRNA) molecules in physiological conditions and their inefficient delivery into the cytoplasm of target cells. Porous silicon nanoparticles have emerged as a potential delivery vehicle to overcome these limitations-being able to encapsulate RNA molecules within the porous matrix and protect them from degradation. Here, key variables were investigated that influence siRNA loading into porous silicon nanoparticles. The effect of modifying the surface of porous silicon nanoparticles with various amino-functional molecules as well as the effects of salt and chaotropic agents in facilitating siRNA loading was examined. Maximum siRNA loading of 413 μg/(mg of porous silicon nanoparticles) was found when the nanoparticles were modified by a fourth generation polyamidoamine dendrimer. Low concentrations of urea or salt increased loading capacity: an increase in RNA loading by 19% at a concentration of 0.05 M NaCl or 21% at a concentration of 0.25 M urea was observed when compared to loading in water. Lastly, it was demonstrated that dendrimer-functionalized nanocarriers are able to deliver siRNA against ELOVL5, a target for the treatment of advanced prostate cancer.

Topics: Dendrimers; Fatty Acid Elongases; Gene Silencing; Gene Transfer Techniques; Humans; Male; Nanoparticles; Polyamines; Porosity; Prostatic Neoplasms; RNA Interference; RNA, Small Interfering; Silicon

Levels of total human kallikrein 2 (hK2), a protein involved the pathology of prostate cancer (PCa), could be used as a biomarker to aid in the diagnosis of this disease. In this study, we report on a porous silicon antibody immunoassay platform for the detection of serum levels of total hK2. The surface of porous silicon has a 3-dimensional macro- and nanoporous structure, which offers a large binding capacity for capturing probe molecules. The tailored pore size of the porous silicon also allows efficient immobilization of antibodies by surface adsorption, and does not require chemical immobilization. Monoclonal hK2 capture antibody (6B7) was dispensed onto P-Si chip using a piezoelectric dispenser. In total 13 × 13 arrays (169 spots) were spotted on the chip with its single spot volume of 300 pL. For an optimization of capture antibody condition, we firstly performed an immunoassay of the P-Si microarray under a titration series of hK2 in pure buffer (PBS) at three different antibody densities (75, 100 and 145 µg/mL). The best performance of the microarray platform was seen at 100 µg/mL of the capture antibody concentration (LOD was 100 fg/mL). The platform then was subsequently evaluated for a titration series of serum-spiked hK2 samples. The developed platform utilizes only 15 µL of serum per test and the total assay time is about 3 h, including immobilization of the capture antibody. The detection limit of the hK2 assay was 100 fg/mL in PBS buffer and 1 pg/mL in serum with a dynamic range of 106 (10(-4) to 10(2) ng/mL).

Topics: Biomarkers, Tumor; Equipment Design; Humans; Immunoassay; Male; Microarray Analysis; Porosity; Prostatic Neoplasms; Silicon; Tissue Kallikreins

In this article we present ultra-sensitive, silicon nanowire (SiNW)-based biosensor devices for the detection of disease biomarkers. An electrochemically induced functionalisation method has been employed to graft antibodies targeted against the prostate cancer risk biomarker 8-hydroxydeoxyguanosine (8-OHdG) to SiNW surfaces. The antibody-functionalised SiNW sensor has been used to detect binding of the 8-OHdG biomarker to the SiNW surface within seconds of exposure. Detection of 8-OHdG concentrations as low as 1 ng/ml (3.5 nM) has been demonstrated. The active device has been bonded to a disposable printed circuit which can be inserted into an electronic readout system as part of an integrated Point of Care (POC) diagnostic. The speed, sensitivity and ease of detection of biomarkers using SiNW sensors render them ideal for eventual POC diagnostics.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antibodies; Biomarkers, Tumor; Biosensing Techniques; Deoxyguanosine; Humans; Male; Nanowires; Prostatic Neoplasms; Silicon

Sensitive and quantitative analysis of proteins is central to disease diagnosis, drug screening, and proteomic studies. Here, a label-free, real-time, simultaneous and ultrasensitive prostate-specific antigen (PSA) sensor was developed using CMOS-compatible silicon nanowire field effect transistors (SiNW FET). Highly responsive n- and p-type SiNW arrays were fabricated and integrated on a single chip with a complementary metal oxide semiconductor (CMOS) compatible anisotropic self-stop etching technique which eliminated the need for a hybrid method. The incorporated n- and p-type nanowires revealed complementary electrical response upon PSA binding, providing a unique means of internal control for sensing signal verification. The highly selective, simultaneous and multiplexed detection of PSA marker at attomolar concentrations, a level useful for clinical diagnosis of prostate cancer, was demonstrated. The detection ability was corroborated to be effective by comparing the detection results at different pH values. Furthermore, the real-time measurement was also carried out in a clinically relevant sample of blood serum, indicating the practicable development of rapid, robust, high-performance, and low-cost diagnostic systems.

Topics: Biomarkers, Tumor; Electrochemistry; Humans; Hydrogen-Ion Concentration; Male; Metal Nanoparticles; Metals; Nanotechnology; Nanowires; Oxides; Prostate-Specific Antigen; Prostatic Neoplasms; Proteomics; Semiconductors; Silicon

In this study, we have used newly developed Silicon nanowire (SiNW) arrays to evaluate their feasibility for the quantification of different markers of interests. We have quantified four different markers of PSA, EGF, IL-6, and VDBP. Each marker showed measurements in the range of 0.184∼17.79 ng/mL (PSA), 10 pg/mL∼10 ng/mL (EGF), 10 pg/mL∼50 ng/mL (IL-6), and 10 pg∼5 ng/mL (VDBP), respectively. For the experiment, we collected 10 different serum samples, 5 prostate cancer patients and 5 breast cancer patients, and measured and compared the resulting signal from the SiNW FET to serum sample from normal patients. As a result, we observed a meaningful pattern of markers associated with each type of cancer. In addition, we have measured the response signal of SiNWs conjugated with Epithelial cell adhesion molecules (EpCAM) markers against tumor cells as they interacted with those markers.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Female; Humans; Immunoassay; Male; Nanowires; Phase Transition; Plastics; Prostatic Neoplasms; Silicon

Dosimetric properties of an amorphous silicon electronic portal imaging device (EPID) for verification of intensity-modulated radiation therapy (IMRT) were investigated as a replacement for conventional verification tools. The portal dosimetry system of Varian's EPID (aS1000) has an integrated image mode for portal dosimetry (PD). The source-to-imager distance was 105 cm, and there were no extra buildup materials on the surface of the EPID in this study. Several dosimetric properties were examined. For clinical dosimetry, the dose distributions of dynamic IMRT beams for prostate cancer (19 patients, 97 beams) were measured by EPID and compared with the results of ionization chamber (IC) measurements. In addition, pretreatment measurements for prostate IMRT (50 patients, 309 beams) were performed by EPID and were evaluated by the gamma method (criterion: 3 mm/3 %). The signal-to-monitor unit ratio of PD showed dose dependence, indicating ghosting effects. Tongue-and-groove effects were observed as a result of the dose difference in the measured EPID images. The results of PD for clinical IMRT beams were in good agreement with the predicted dose image with average values of 1.37 and 0.25 for γ (max) and γ (ave), respectively. The point doses of PD were slightly, but significantly, higher than the results of IC measurements (p < 0.05 paired t test). However, this small difference seems clinically acceptable. This portal dosimetry system is useful as a rapid and convenient verification tool for dynamic IMRT.

Topics: Electrical Equipment and Supplies; Humans; Male; Prostatic Neoplasms; Quality Control; Radiometry; Radiotherapy Dosage; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Signal-To-Noise Ratio; Silicon

Topics: Breast Neoplasms; Complex Mixtures; Equipment Design; Female; Humans; Male; Microfluidics; Molecular Imaging; Nanostructures; Neoplastic Cells, Circulating; Prostatic Neoplasms; Silicon; Surface Properties

Nanowire field-effect transistors (NW-FETs) are emerging as powerful sensors for detection of chemical/biological species with various attractive features including high sensitivity and direct electrical readout. Yet to date there have been limited systematic studies addressing how the fundamental factors of devices affect their sensitivity. Here we demonstrate that the sensitivity of NW-FET sensors can be exponentially enhanced in the subthreshold regime where the gating effect of molecules bound on a surface is the most effective due to the reduced screening of carriers in NWs. This principle is exemplified in both pH and protein sensing experiments where the operational mode of NW-FET biosensors was tuned by electrolyte gating. The lowest charge detectable by NW-FET sensors working under different operational modes is also estimated. Our work shows that optimization of NW-FET structure and operating conditions can provide significant enhancement and fundamental understanding for the sensitivity limits of NW-FET sensors.

Topics: Biosensing Techniques; Humans; Hydrogen-Ion Concentration; Male; Nanoparticles; Nanostructures; Nanotechnology; Nanowires; Poisson Distribution; Prostate-Specific Antigen; Prostatic Neoplasms; Proteins; Silicon; Temperature; Thermodynamics

Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid-polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications.

Topics: Animals; Cell Line, Tumor; Coated Materials, Biocompatible; Female; Ferric Compounds; Fluorescent Dyes; Humans; Macrophages; Magnetics; Male; Mice; Molecular Imaging; Optical Phenomena; Prostatic Neoplasms; Quantum Dots; Silicon

The generation of high quality plasma from whole blood is of major interest for many biomedical analyses and clinical diagnostic methods. However, it has proven to be a major challenge to make use of microfluidic separation devices to process fluids with high cell content, such as whole blood. Here, we report on an acoustophoresis based separation chip that prepares diagnostic plasma from whole blood linked to a clinical application. This acoustic separator has the capacity to sequentially remove enriched blood cells in multiple steps to yield high quality plasma of low cellular content. The generated plasma fulfills the standard requirements (<6.0 x 10(9) erythrocytes/L) recommended by the Council of Europe. Further, we successfully linked the plasmapheresis microchip to our previously developed porous silicon sandwich antibody microarray chip for prostate specific antigen (PSA) detection. PSA was detected by good linearity (R(2) > 0.99) in the generated plasma via fluorescence readout without any signal amplification at clinically relevant levels (0.19-21.8 ng/mL).

Topics: Antibodies, Monoclonal; Erythrocytes; Female; Humans; Immunoassay; Male; Microarray Analysis; Microfluidic Analytical Techniques; Plasmapheresis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Array Analysis; Silicon

The gastrin-releasing peptide receptor (GRPr) is overexpressed on various human tumors. The goal of our study was the synthesis of new 18F-labeled bombesin analogues for the PET imaging of GRPr expression in prostate tumor using a silicon-based one-step n. c. a. radiolabeling method. The silicon-containing building blocks were efficiently coupled to the N-terminus of the peptides via solid-phase synthesis. Radiolabeling of the obtained peptide precursors proceeded smoothly under acidic conditions (34-85% conversion). Using the di-tert-butyl silyl building block as labeling moiety, products containing a hydrolytically stable 18F-label were obtained. In in vitro receptor binding experiments 2-(4-(di-tert-butylfluorosilyl)phenyl)acetyl-Arg-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH 2 ( 4b, IC50 = 22.9 nM) displayed a 12-fold higher binding affinity than 2-(4-(di-tert-butylfluorosilyl)phenyl)acetyl-Arg-Ava-Gln-Trp-Ala-Val-Gly-His(3Me)-Sta-Leu-NH2 ( 3b, IC50 = 276.6 nM), and 4b was therefore chosen for further evaluation. In vitro and ex vivo metabolite studies of [18F]4b showed no significant degradation. In biodistribution experiments, tumor uptake of [18F]4b was low and unspecific, whereas the GRPr-rich pancreas revealed a high and specific accumulation of the radiotracer. This study demonstrates the applicability of our silicon-based one-step n. c. a. radiolabeling method for the synthesis of new 18F-labeled bombesin derivatives. This innovative approach represents a general, straightforward access to radiolabeled peptides as PET imaging probes.

Topics: Amino Acid Sequence; Binding Sites; Bombesin; Fluorine Radioisotopes; Humans; Isotope Labeling; Male; Molecular Sequence Data; Neurotransmitter Agents; Positron-Emission Tomography; Prostatic Neoplasms; Receptors, Bombesin; Silicon; Substrate Specificity

When dose delivery to the patient is evaluated by extracting the primary photon fluence impinging on a portal imaging device, scattered radiation from the patient acts as noise. Our aim in the present study is to establish and test a procedure to filter out scatter radiations from portal images by experimental determination of a scatter filtering function. We performed a dose calibration of the Varian (Varian Medical Systems, Palo Alto, CA) aS500 electronic portal imaging device in routine use in our institution. We then analyzed the collected data and extracted the scatter filtering function by applying a simple scatter model with the aid of home-made software. To check the reliability of our calculations we compared central axis dose values in a PMMA phantom computed using the extracted primary fluence with those obtained from experimental TMR(0) tabulated values obtaining a agreement within about 3%. We finally performed a check of dose delivery repeatability by calculating the dose delivered to the EPID during portal image acquisition for patient positioning. Delivered dose per MU fluctuations were within 5% over a set of images acquired during routine use with no prior application of any procedure aimed at optimizing dosimetric repeatability.

Topics: Algorithms; Calibration; Humans; Male; Phantoms, Imaging; Photons; Prostatic Neoplasms; Radiation Dosage; Radiographic Image Enhancement; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Reproducibility of Results; Retrospective Studies; Scattering, Radiation; Silicon; Software

For EPID dosimetry, the calibration should ensure that all pixels have a similar response to a given irradiation. A calibration method (MC), using an analytical fit of a Monte Carlo simulated flood field EPID image to correct for the flood field image pixel intensity shape, was proposed. It was compared with the standard flood field calibration (FF), with the use of a water slab placed in the beam to flatten the flood field (WS) and with a multiple field calibration where the EPID was irradiated with a fixed 10x10 field for 16 different positions (MF). The EPID was used in its normal configuration (clinical setup) and with an additional 3 mm copper slab (modified setup). Beam asymmetry measured with a diode array was taken into account in MC and WS methods. For both setups, the MC method provided pixel sensitivity values within 3% of those obtained with the MF and WS methods (mean difference<1%, standard deviation<2%). The difference of pixel sensitivity between MC and FF methods was up to 12.2% (clinical setup) and 11.8% (modified setup). MC calibration provided images of open fields (5x5 to 20x20 cm2) and IMRT fields to within 3% of that obtained with WS and MF calibrations while differences with images calibrated with the FF method for fields larger than 10x10 cm2 were up to 8%. MC, WS and MF methods all provided a major improvement on the FF method. Advantages and drawbacks of each method were reviewed.

Topics: Calibration; Head and Neck Neoplasms; Humans; Male; Monte Carlo Method; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted; Silicon

An on-line system to ensure accuracy of daily setup and therapy of the prostate has been implemented with no equipment modification required. We report results and accuracy of patient setup using this system.. Radiopaque fiducial markers were implanted into the prostate before radiation therapy. Lateral digitally reconstructed radiographs (DRRs) were obtained from planning CT data. Before each treatment fraction, a lateral amorphous silicon (aSi) portal image was acquired and the position of the fiducial markers was compared to the DRRs using chamfer matching. Couch translation only was used to account for marker position displacements, followed by a second lateral portal image to verify isocenter position. Residual displacement data for the aSi and previous portal film systems were compared.. This analysis includes a total of 239 portal images during treatment in 17 patients. Initial prostate center of mass (COM) displacements in the superior, inferior, anterior, and posterior directions were a maximum of 7 mm, 9 mm, 10 mm and 11 mm respectively. After identification and correction, prostate COM displacements were <3 mm in all directions. The therapists found it simple to match markers 88% of the time using this system. Treatment delivery times were in the order of 9 min for patients requiring isocenter adjustment and 6 min for those who did not.. This system is technically possible to implement and use as part of an on-line correction protocol and does not require a longer than standard daily appointment time at our center with the current action limit of 3 mm. The system is commercially available and is more efficient and user-friendly than portal film analysis. It provides the opportunity to identify and accommodate interfraction organ motion and may also permit the use of smaller margins during conformal prostate radiotherapy. Further integration of the system such as remote table control would improve efficiency.

Topics: Humans; Male; Movement; Online Systems; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Silicon; Software; Tomography, X-Ray Computed

Online prostate positioning using gold markers and a standard video-based electronic portal imaging device is reported. The average systematic (random) errors have been reduced from 2.1 mm (2.7 mm) to 0.5 mm (1.5 mm) in AP direction, 1.1 mm (1.7 mm) to 0.7 mm (1.2 mm) SI and 1.2 mm (1.7 mm) to 0.6 mm (1.3 mm) LR.

Topics: Algorithms; Electronics, Medical; Humans; Male; Prostatic Neoplasms; Radiotherapy; Silicon

Here we study automatic detection of implanted gold markers relative to the field boundary in portal images for on-line position verification. Portal images containing 1-2 MU were taken with an amorphous silicon flat-panel imager. The images were obtained with lateral field at 18 MV. Both the detection success rate and the localization accuracy of markers of 1.0 and 1.2 mm diameter were determined with the help of a marker detection method based on a marker extraction kernel. A method for determining a fiducial reference point related to the field boundary was developed. Detection success rates were 0.99, 0.90 and 0.95 for markers of 1.2 mm diameter and 5 mm length, 1.0 mm diameter and 5 mm length and 1.0 mm diameter and 10 mm length respectively. The localization accuracy appeared to be better than 0.3 mm. The reference point could be reproduced with an accuracy equal to 1 pixel (0.5 mm at isocentre) within one fraction. During the first few seconds of a treatment fraction the field edge was not stable, which appeared to be an effect of the motion of the radiation source. Thanks to the use an a-Si flat-panel imager, on-line position verification using implanted gold markers becomes clinically feasible. We can use a clinically acceptable marker diameter as small as 1.0 mm. These markers can be automatically detected in portal images obtained with 1-2 MU relative to a stable reference point related to the field boundary.

Topics: Algorithms; Gold; Humans; Implants, Experimental; Male; Prostate; Prostatic Neoplasms; Radiography; Radiotherapy, Conformal; Silicon

Topics: Humans; Male; Prostatic Neoplasms; Radiotherapy, High-Energy; Silicon; Urinary Sphincter, Artificial

Topics: Elementary Particles; Energy Transfer; Humans; Male; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neoplasms; Prostatic Neoplasms; Radiometry; Radiotherapy Dosage; Silicon

Topics: Aged; Chromium; Chromium Alloys; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Norway; Occupational Diseases; Prostatic Neoplasms; Silicon; Silicon Compounds