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.

A new 2 methylalanine-PVC ESR dosimeter.

The use of polyvinyl chloride (PVC) as a binder to 2-methylalanine (2MA) dosimeters was investigated. It was recently shown by Olsson et al. (Radiat. Res. 157 (2002) 113), that 2MA is approximately 70% more sensitive than L-alanine which makes this substance a good candidate to replace alanine in ESR dosimetry. PVC is a low yield material for free radical production by ionizing radiation and a good binding material easily processed and widely available. PVC can be prepared at room temperature and mixed up to 50% in weight with 2MA to produce a pellet stable in mass and physical dimensions, in large quantities and with low background signal. Pure PVC pellet irradiated at 50 Gy gave weaker ESR signals compared to 2MA at the region of spectral interest. Spectrometer settings such as microwave power, and modulation amplitude were optimized for the measurements. This dosimeter production scheme allows the addition of Mn2+ ions for an internal reference signal, leading to a self-calibrated dosimeter (J. Radional. Nucl. Chem. 240 (1999) 215).

Electron spin-lattice relaxation in radicals containing two methyl groups, generated by gamma-irradiation of polycrystalline solids.

The effects of methyl rotation on electron spin-lattice relaxation times were examined by pulsed electron paramagnetic resonance for the major radicals in gamma-irradiated polycrystalline alpha-amino isobutyric acid, dimethyl-malonic acid, and L-valine. The dominant radical is the same in irradiated dimethyl-malonic acid and alpha-amino isobutyric acid. Continuous wave saturation recovery was measured between 10 and 295 K at S-band and X-band. Inversion recovery, echo-detected saturation recovery, and pulsed electron-electron double resonance (ELDOR) data were obtained between 77 and 295 K. For the radicals in the three solids, recovery time constants measured by the various techniques were not the same, because spectral diffusion processes contribute differently for each measurement. Hyperfine splitting due to the protons of two methyl groups is resolved in the EPR spectra for each of the samples. Pulsed ELDOR data were obtained to characterize the spectral diffusion processes that transfer magnetization between hyperfine lines. Time constants were obtained for electron spin-lattice relaxation (T(1e)), nuclear spin relaxation (T(1n)), cross-relaxation (T(x1)), and spin diffusion (T(s)). Between 77 and 295 K rapid cross-relaxation (deltaM(s) = +/- 1, deltaM(I) = -/+ 1) was observed for each sample, which is attributed to methyl rotation at a rate that is approximately equal to the electron Larmor frequency. The large temperature range over which cross-relaxation was observed suggests that methyl groups in the radical and in the lattice, with different activation energies for rotation, contribute to the rapid cross-relaxation. Activation energies for methyl and amino group rotation between 160 and 1900 K (1.3-16 kJ/mol) were obtained by analysis of the temperature dependence of 1/T(1e) at S-band and X-band in the temperature intervals where the dynamic process dominates T(1e).

EPR dosimetric properties of 2-methylalanine: EPR, ENDOR and FT-EPR investigations.

To find an EPR dosimeter material that is sensitive enough for clinical use, the substance 2-methylalanine (2MA) with the chemical structure (CH(3))(2)C(NH(3)(+))COO(-) was tested for its sensitivity to ionizing radiation, dose response, and radical stability over time. At equal and moderate settings of microwave power and modulation amplitude, 2MA was found to be 70% more sensitive than L-alpha-alanine, which is the most common EPR dosimeter material today. The dose response is linear, at least in the dose range of interest (0.5-00 Gy), and the time-dependent variations in signal intensity are very small and may be corrected for easily. The energy dependence of the stopping power and energy absorption was calculated and was found to be similar to that of alanine. The dependence of the signal intensity on microwave power and modulation amplitude was investigated, and the optimal settings were found to be 25 mW (Bruker ER 4102ST) and 12 gauss, respectively. Single crystals of 2MA were analyzed using ENDOR and ENDOR-induced EPR to identify the radiation-induced radicals that formed. Only one radical, in which the amino group is detached from the original molecule, was identified. This radical is obviously dominating and is apparently the only one relevant for dosimetry purposes. The complete set of coupling parameters for three hyperfine couplings is reported. The power saturation properties and spectral line width are ruled by the relaxation times T(1) and T(2). To determine the relaxation times of 2MA, pulsed EPR experiments were performed on single crystals. Two different values of T(1) were obtained, one in the range 1-3 micros, shown to be of importance for the dosimetry properties, and another that is strongly anisotropic with a value between 10 and 35 micros that does not seem to affect the saturation behavior. T(2) was estimated to be of the order of 200-300 ns.