P Nicolucci

Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo.

UNLABELLED We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach. FROM THE CLINICAL EDITOR The ability of gold nanoparticles (AuNPs) to enhance the effect of physical radiation dose on tumor cells is known. This radiosensitization effect is thought to result from an increased number of photoelectric absorption events and the increased number of electrons present in gold. The authors here sought to further increase the amount and specificity of gold accumulation in prostatic cancer cells by conjugating gold nanorods to goserelin, a synthetic luteinizing hormone releasing hormone (LHRH) analogue that would bind to the LHRH receptor overexpressed in prostate cancers. It was shown that tumour cells were more sensitive to megavoltage radiation therapy. It is hoped that there would be eventual clinical translation of this approach.

Low dose ionizing radiation detection using conjugated polymers

In this work, the effect of gamma radiation on the optical properties of poly[2-methoxy-5-(2′-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) is studied. The samples were irradiated at room temperature with different doses from 0Gyto152Gy using a Co60 gamma ray source. For thin films, significant changes in the UV-visible spectra were only observed at high doses (>1kGy). In solution, shifts in absorption peaks are observed at low doses (<10Gy), linearly dependent on dose. The shifts are explained by conjugation reduction, and possible causes are discussed. Our results indicate that MEH-PPV solution can be used as a dosimeter adequate for medical applications.

Synthesis and characterization of gold/alanine nanocomposites with potential properties for medical application as radiation sensors.

Radiation dose assessment is essential for several medical treatments and diagnostic procedures. In this context, nanotechnology has been used in the development of improved radiation sensors, with higher sensitivity as well as smaller sizes and energy dependence. This paper deals with the synthesis and characterization of gold/alanine nanocomposites with varying mass percentage of gold, for application as radiation sensors. Alanine is an excellent stabilizing agent for gold nanoparticles because the size of the nanoparticles does not augment with increasing mass percentage of gold, as evidenced by UV-vis spectroscopy, dynamic light scattering, and transmission electron microscopy. X-ray diffraction patterns suggest that the alanine crystalline orientation undergoes alterations upon the addition of gold nanoparticles. Fourier transform infrared spectroscopy indicates that there is interaction between the gold nanoparticles and the amine group of the alanine molecules, which may be the reason for the enhanced stability of the nanocomposite. The application of the nanocomposites as radiation detectors was evaluated by the electron spin resonance technique. The sensitivity is improved almost 3 times in the case of the nanocomposite containing 3% (w/w) gold, so it can be easily tuned by changing the amount of gold nanoparticles in the nanocomposites, without the size of the nanoparticles influencing the radiation absorption. In conclusion, the featured properties, such as homogeneity, nanoparticle size stability, and enhanced sensitivity, make these nanocomposites potential candidates for the construction of small-sized radiation sensors with tunable sensitivity for application in several medical procedures.

Gel Dosimetry Analysis of Gold Nanoparticle Application in Kilovoltage Radiation Therapy

In this work gold nanoparticles (AuNP) were embedded in MAGIC-f gel and irradiated in a 250 kV x-ray clinical beam. The signal of non-irradiated gel samples containing AuNPs showed maximum difference of 0.5% related to gel without nanoparticles. Different AuNPs concentrations were studied: 0.10 mM, 0.05 mM and 0.02 mM, presenting dose enhancements of 106%, 90% and 77% respectively. Monte Carlo spectrometry was performed to quantify theoretical changes in photon energy spectrums due to AuNPs presence. Concordance between simulated dose enhancements and gel dosimetry measurements was better than 97% to all concentrations studied. This study evidences that polymer gel dosimetry as a suitable tool to perform dosimetric investigations of nanoparticle applications in Radiation Therapy.

Spatial resolution of magnetic resonance imaging Fricke-gel dosimetry is improved with a honeycomb phantom.

The spatial accuracy of magnetic resonance imaging (MRI) Fricke-gel dosimetry is limited by diffusion of ferric ions. This paper describes a honeycomb structure to limit diffusion of Fe3+ ions in a three-dimensional phantom. Such a phantom containing the dosimeter gel was irradiated to a known dose distribution. Maps of dose distributions were produced from the MR images acquired at 2 and 24 hours after the dose was given. The dose distribution maps verified that the honeycomb structure precludes ion diffusion from one honeycomb cell to another, thus improving the usefulness of MRI Fricke-gel dosimetry.

Sensitivity comparison of two L-alanine doped blends to different photon energies.

Blends of L-alanine (85% weight proportion) with KI (10%) and with PbI2 (10%), these last two compounds acting as dopants, and with PVA (5%) acting as binder, were prepared in water at 80°C. A blend of pure L-alanine (95%) with PVA (5%) was also prepared. The three blends were irradiated with photon beams of different energies (120 kV, 60Co, and 10 MV) to a unique dose of 30 Gy to compare their sensitivities for those three energies. EPR spectra of the three irradiated blends were recorded in a K-Band spectrometer (24 GHz) taking aliquots of about 4 mg for each blend. The energy sensitivity of a blend was defined as the peak-to-peak amplitude of its EPR spectrum central line. For the 60Co energy (1.25 MeV) the blends presented practically the same sensitivity, indicating that the presence of the dopants does not affect the sensitivity of L-alanine. For 10 MV x-rays, there was an increment (around 10%–20%) in sensitivity for the two L-alanine doped blends compared with the pure L-alanine blend (not doped). In the case of 120 kV x-rays, the blends ala+KI and ala+PbI showed increments of 10 and 20 times more sensitivity than the pure L-alanine blend. It is concluded that the dopants KI and PbI2 produce a great enhancement of the L-alanine sensitivity to low-energy photons. For the same dopants content (10%) in the blend, PbI2 showed a better performance. Increasing the PbI2 proportion (30%) in the blend allows the detection of radiation dose as low as 10 mGy for 120 kV x-rays. These results encourage the authors to try to enhance the sensitivity of L-alanine even more by increasing the dopants content in the blend and diminishing the lower limit detection. Application of these L-alanine doped blends in the dosimetry in diagnostic radiology could be possible.

Influence of Dental Restorative Materials on ESR Biodosimetry in Tooth Enamel

Using an experimental model and PENELOPE Monte Carlo simulations, the effects of resin and amalgam on the absorbed doses in tooth enamel were studied to evaluate the feasibility of using restored teeth in electron spin resonance (ESR) dose reconstruction. The model consisted of a phantom containing a plate of these restorative materials placed between powered enamel layers exposed to X rays and a 60Co beam. The experimental results and simulations agreed, showing that the attenuation produced by amalgam and resin with a thickness of 1, 2, and 4 mm is similar to that produced by the enamel itself in the case of the radiation sources employed. For X rays and 60Co &ggr; radiation the attenuation reached almost 100% and 40%, respectively. These results show that for ESR dose reconstruction, the use of all available enamel of a tooth leads to errors in the estimated dose due to attenuation effects in both healthy and restored teeth. Thus the importance of an enamel selection from different sides of the tooth surface to apply ESR dose reconstruction in the case of a practical situation is shown.

Dosimetric properties of MAGIC-f polymer gel assessed to Radiotherapy clinical beams

Dosimetric properties of MAGIC-f gel were studied for a wide range of beams used in Radiotherapy. The MAGIC-f tissue-equivalence was theoretically verified using PENELOPE Monte Carlo code and experimentally by percentage depth dose curves for water and gel (maximum differences of 2.0% and 0.5% for 6MV and 10MV, respectively). Energy and dose-rate dependency were evaluated in a range from 60 kV to 10 MV and 0.44 Gy/min to 10 Gy/min respectively. MAGIC-f presents linearity to all energies studied and its sensitivity presents maximum and average variation of 8.6% and 7.7% respectively in the range of energy considered. The study of dose rate dependency evidence that MAGIC-f presents no significant variation of response in clinical intervals of dose rate: lower than 0.7% when x-ray are considered and lower than 1.9% when all beams are considered. Its dosimetric characteristics indicate that MAGIC-f is a very suitable dosimeter for Radiotherapy.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gels response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Experimental assessment of gold nanoparticle-mediated dose enhancement in radiation therapy beams using electron spin resonance dosimetry

In this work, we aim to experimentally assess increments of dose due to nanoparticle-radiation interactions via electron spin resonance (ESR) dosimetry performed with a biological-equivalent sensitive material.We employed 2-Methyl-Alanine (2MA) in powder form to compose the radiation sensitive medium embedding gold nanoparticles (AuNPs) 5 nm in diameter. Dosimeters manufactured with 0.1% w/w of AuNPs or no nanoparticles were irradiated with clinically utilized 250 kVp orthovoltage or 6 MV linac x-rays in dosimetric conditions. Amplitude peak-to-peak (App) at the central ESR spectral line was used for dosimetry. Dose-response curves were obtained for samples with or without nanoparticles and each energy beam. Dose increments due to nanoparticles were analyzed in terms of absolute dose enhancements (DEs), calculated as App ratios for each dose/beam condition, or relative dose enhancement factors (DEFs) calculated as the slopes of the dose-response curves.Dose enhancements were observed to present an amplified behavior for small doses (between 0.1-0.5 Gy), with this effect being more prominent with the kV beam. For doses between 0.5-5 Gy, dose-independent trends were observed for both beams, stable around (2.1   ±   0.7) and (1.3   ±   0.4) for kV and MV beams, respectively. We found DEFs of (1.62   ±   0.04) or (1.27   ±   0.03) for the same beams. Additionally, we measured no interference between AuNPs and the ESR apparatus, including the excitation microwaves, the magnetic fields and the paramagnetic radicals.2MA was demonstrated to be a feasible paramagnetic radiation-sensitive material for dosimetry in the presence of AuNPs, and ESR dosimetry a powerful experimental method for further verifications of increments in nanoparticle-mediated doses of biological interest. Ultimately, gold nanoparticles can cause significant and detectable dose enhancements in biological-like samples irradiated at both kilo or megavoltage beams.