How do monomeric components of a polymer gel dosimeter respond to ionising radiation: A steady-state radiolysis towards preparation of a 3D polymer gel dosimeter

Ionising radiation-induced reactions of aqueous single monomer solutions and mixtures of poly(ethylene glycol) diacrylate (PEGDA) and N,N′-methylenebisacrylamide (Bis) in a steady-state condition are presented below and above gelation doses in order to highlight reactions in irradiated 3D polymer gel dosimeters, which are assigned for radiotherapy dosimetry. Both monomers are shown to undergo radical polymerisation and cross-linking, which result in the measured increase in molecular weight and radius of gyration of the formed polydisperse polymer coils. The formation of nanogels was also observed for Bis solutions at a low concentration. In the case of PEGDA-Bis mixtures, co-polymerisation is suggested as well. At a sufficiently high radiation dose, the formation of a polymer network was observed for both monomers and their mixture. For this reason a sol–gel analysis for PEGDA and Bis was performed gravimetrically and a proposition of an alternative to this method employing a nuclear magnetic resonance technique is made. The two monomers were used for preparation of 3D polymer gel dosimeters having the acronyms PABIG and PABIG^nx. The latter is presented for the first time in this work and is a type of the formerly established PABIG polymer gel dosimeter. The elementary characteristics of the new composition are presented, underlining the ease of its preparation, low dose threshold, and slightly increased sensitivity but lower quasi-linear range of dose response in comparison to PABIG.     

Dose distribution verification in intraoperative radiation therapy using an N-isopropyl acrylamide-based polymer gel dosimeter

The purpose of the current study was to verify the dose distribution of an Intrabeam-50 kV IORT system using polymer gel dosimetry technique. Results of dose distribution evaluation using NIPAM polymer gel dosimetry were compared with those measured using an ionization chamber and simulated using MCNPX code. Results showed the calculated gamma index was less than 1 with 2% dose-difference/2 mm distance-to-agreement for comparison between NIPAM and ionization chamber as well as between NIPAM and MCNPX simulation. It was concluded that the NIPAM polymer gel dosimetry is useful for verifying the dose distribution of low energy X-ray IORT technique.

     

Optimal composition of a new polymer gel dosimeter-DEMBIG

Polymeric gel dosimeters are used to verify three-dimensional (3D) dose distributions of various types of radiotherapy treatments, particularly radiosurgery. The present paper investigates the low toxicity and high dose response of a new acrylate gel. The optimal recipe with the best linearity (R ² = 0.998) is 7% gelatin, 5% 2-(dimethylamino) ethyl acrylate monomer, and 4% N′N′-methylene-bisacrylamide crosslinker. The dose range is 0–30 Gy, and the temporal stability time is 12 h after irradiation. No significant energy dependency has been observed. The results show that the 2-(dimethylamino) ethyl acrylate N′N′-methylene-bisacrylamide gelatin gel is a potential 3D dosimeter.     

Dose verification of volumetric modulation arc therapy by using a NIPAM gel dosimeter combined with a parallel-beam optical computed tomography scanner

Volumetric modulated arc therapy (VMAT) was developed to shorten treatment time and increase target conformance. However, a true three-dimensional (3D) gel dosimeter is needed for dose verification. In this study, two clinic cases were adopted: a simple case of lung cancer and a complex case of larynx cancer. For each clinic case, two treatment plans were generated for the same planning target volume using VMAT and intensity modulated radiation therapy calculation software packages. An N-isopropylacrylamide (NIPAM) polymer gel dosimeter was used for 3D dose verification. In addition, the dose characteristics of the NIPAM gel dosimeter were investigated for the two clinic cases.

     

An approach in exploring the fundamental dosimetric characteristics for a long shelf life irradiated acrylamide-based gel

In this study, a long shelf life irradiated gel made from a low-toxicity N-isopropylacrylamide (NIPAM) monomer was used to study the dosimetric characteristics associated with magnetic resonance imaging (MRI). Specifically, the Taguchi method was utilized to investigate the influence of MRI scanning parameters on the performance objectives of NIPAM gels, and the priorities of the parameters that influence the process were determined using Delta statistics. The influence of different echo spacing on the relaxation rate–dose response of the gel and the relationship among the dose resolution (D _Δ ^P ), dose accuracy, and reproducibility were also examined. The results indicated that the repetition time (TR) and echo time (TE), having Delta values of 3.81042 and 4.52752, respectively, were the most influential factors. Analysis of variance further confirmed that TE was the major factor, with a percentage contribution of 58.36 %, and TR was the second factor with a percentage contribution of 41.34 %. The maximum sensitivity was 0.1506 s^?1 Gy^?1 from 0 to 15 Gy, and the best D _Δ ^P of the NIPAM gel was 0.017 Gy. Two months after the irradiation, no obvious changes in linearity and sensitivity were observed, indicating that the NIPAM gels are highly stable. The gel dosimeters were also applied in comparing the planar dose distributions of the gel dosimeters and treatment planning system. The comparison showed good agreement of isodose lines on selected planes in the transverse plane. This result indicates the great potential of the NIPAM dosimeter has a clinical dose verification tool.     

Characterization of long-term dose stability of N-isopropylacrylamide polymer gel dosimetry

In this study, the detailed characteristics, including spatial uniformity, dose distributions, inter-batch variability, reproducibility, and long-term temporal stability, of N-isopropylacrylamide (NIPAM) polymer gel dosimeter were investigated. A commercial 10x fast optical computed tomography scanner (OCTOPUS^TM-10×, MGS Research, Inc., Madison, CT, USA) was used to measure NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom that measured 10 cm × 10 cm was irradiated via a single-field treatment plan with a field size of 4 cm × 4 cm. The maximum standard deviation of spatial uniformity for NIPAM gel was less than 0.29 %. The average standard deviation among the three batches of gel dosimeters was less than 1 %. The gamma pass rate could reach as high as 96.76 % when a 3 % dose difference and a 3 mm dose-to-agreement criteria were used. The long-term measurement of irradiated NIPAM gel dosimeter indicated that the dose maps attained a gradually stable value 15 h post-irradiation and remained stable until 72 h post-irradiation. The gamma pass rate could achieve a maximum value between 24 and 72 h post-irradiation. The edge enhancement effect that occurred around the irradiated region was observed 72 h post-irradiation. Thus, the results from this study suggest that NIPAM gel dosimeter should be measured approximately 24 h post-irradiation to reduce the occurrence of the edge enhancement effect.     

Synthetic thermally reversible gel systems. VI

Forming and conditioning thermally reversible aqueous gels of polyacrylyglycinamide (PAG) at various temperatures has little effect on either the melting point (T_m) of the gels or the heat of crosslinking (ΔH_c) except at temperatures where partial hydrolysis can occur. This is added evidence that unlike with gelatin, crystallite formation does not play a role in gel formation. For unfractioned PAG, the linear relationship between the logarithm of molecular weight and 1/T_m predicted and observed for gelatin gels, does not hold. With mixed gelatin-PAG gels, a gelatin/PAG ratio of ≥4 completely inhibits the formation of a PAG gel network. At lower gelatin/PAG ratios, the PAG network forms, and if gelatin is considered as an inert diluent, normal values for the melting points and ΔH_c for PAG gels are observed. At a gelatin/PAG ratio of 4, the presence of PAG reduces the ΔH_c for the gelatin gel by inhibiting the formation of as large or as ordered crystallite crosslinks. To reconcile the problem of aggregation preceding gelation one can assume that M?_w of an aggregate is a linear function of C². If this is done, the same relationship which normally relates C with T_m is obtained. The equilibrium swelling of PAG films in water at 25°C is markedly molecular weight-de-pendent and can vary from below 5 to about 40 wt-% polymer at equilibrium. It has been found that long-term dark storage of dry samples of PAG under ambient temperature conditions results in pronounced decreases in the intrinsic viscosities of their aqueous solutions. It is speculated that this results from weak links, perhaps peroxy, in the polymer backbone. The possible relationship of this phenomenon to the slow stage of the viscosity deterioration of aqueous polyacrylamide solutions is pointed out. The higher viscosity of low DP PAG in 2M NaCNS compared to H₂O and the larger percentage increse of [η] with increasing temperature in the latter, verify the greater solvent power of 2M aqueous thiocyanate for PAG. At a concentration level of 3%, aqueous PAG solutions are almost Newtonian whereas at higher concentrations (5%), the viscosity decreases appreciably with increasing rates of shear. The copolymerization of AG with isopropylacrylamide has been studied and the somewhat unusual results discussed. Copolymers containing an AG mole fraction greater than 0.40 do not exhibit a cloud point up to 100°C. If the isopropylacrylamide mole fraction approaches 0.60, the solutions do not gel down to 0°C. This ability to prepare copolymers over a narrow composition range that neither gel or undergo phase separation in the temperature range 0–100°C is probably related to the random distribution of monomer units in the copolymer backbone.     

Dispersion of silica nanoparticles bearing perfluorohexyl units into fluorinated copolymers

This study aims at determining the compatibility behavior of nanoparticles surface with fluorinated matrices to obtain a homogenous dispersion and better composites properties. First, modified silica nanoparticles by C₆F₁₃I and C₆F₁₃‐C₂H₄‐SH led to various fluorinated silica of different massic concentrations and grafting rates. The dispersion of these nanoparticles (in 5 wt %) into molten poly(VDF‐co‐HFP) and poly(TFE‐co‐HFP) matrices were studied as well as the hydrophobic, mechanical, and thermal properties of both fluorinated copolymers and resulting composites. In both series, the storage modulus of nanocomposites increased while the melting (T_m) and decomposition (T_10%) temperatures varied with the polymer matrix. They increased for poly(VDF‐co‐HFP) composites (T_m= 134 to 144 °C and T_10%= 441 to 464 °C) but decreased for poly(TFE‐co‐HFP) nanocomposites (T_m= 276 to 268 °C and T_10%= 488 to 477 °C). © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1512–1522     

Dielectric behaviour of Gelatin solutions and Gels

 Sol and Gel state properties of aqueous gelatin solutions of concentrations 4%, 6%, 8% and 10% (w/v) have been investigated through dielectric relaxation studies done at various temperatures in the range T=20–60 °C carried out over a frequency range f=20 Hz–10 MHz and no relaxation of any nature was observed. The sharp transition observed at the gelation temperature T _gel provided an excellent matching with the same measured through differential scanning calorimetry (DSC). The capacitance (C _p) values above f=100 kHz became increasingly negative as the gel was melted to the sol state. However, in the gel state C _p was found to be almost independent of temperature for frequencies above 100 kHz. At frequencies lower than 10 kHz, C _p measured was ∼10⁵ F, implying pronounced interfacial polarization either due to electro-chemical reaction or because of ions getting trapped at some interface within the bulk. Received: 10 February 1997 Accepted: 2 September 1997     

Effects of phenolic compounds on gelation behavior of gelatin gels

The effects of phenolic additives on the gelation behavior of gelatin gels were investigated using thermomechanical analysis (TMA) for study of gel‐melting temperature, dynamic mechanical analysis (DMA) for study of gel‐storage modulus and gel‐aging stability, viscometry for study of gelation time, and texture analyzer for study of gel strength and gel melting. Thermodynamically, the addition of 1,3‐benzenediol, 1,4‐benzenediol or 1,3,5‐benzenetriol favored the gelation process of gelatin solutions (increases in T_m and aging stability) due to the introduction of extra physical crosslinks among gelatin chains through hydrogen bonding, while the addition of 1,2‐benzenediol had a negative effect (decreases in T_m and aging stability) possibly due to intra‐hydrogen bonding of the additive molecule itself. All the phenolic compounds had little effect on gel moduli. Kinetically, the introduction of 1,2‐benzenediol or 1,4‐benzenediol slowed the gelation process, while introduction of catechin, a polyphenol, accelerated the first stage of the gelation process. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 224–231, 2001     

Synthesis and phase behavior of aqueous poly(N-isopropylacrylamide-co-acrylamide), poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate)

Poly(N-isopropylacrylamide) (PNIPAM) and random copolymers of Poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNIPAM-HEMA), poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAm), and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PNIPAM-DMAA) with various volume fractions γ of NIPAM were synthesized by radical polymerization. The phase behavior of the polymers in water was investigated by means of optical transmittance and dynamic light scattering. With decreasing γ, the cloud point temperature T _cp for PNIPAM-HEMA decreased whereas the T _cp for both PNIPAM-AAm and PNIPAM-DMAA increased. Increase of hydrodynamic radius around T _cp, which resulted from the aggregation of the globules of each polymer, was observed from dynamic light scattering. The relationships between the reciprocal of T _cp of the polymer solutions and 1-γ were linear for the three copolymers in the experimental range of 0.65<γ<1. The results are discussed from the aspect of the interaction parameters of copolymer solutions.     

Optical and MRI investigations of an optimized acrylamide-based polymer gel dosimeter

The first purpose of this research was improvement of sensitivity of the normoxic acrylamide-based polymer gel dosimeter. Another aim of this study was investigation of the absorbance of the irradiated gels as well as their relaxation rate variations. In addition, a new optical parameter, area under the absorbance spectrum (AUS), was investigated. Sensitivity improvement was performed by adding glucose and urea to the previously reported acrylamide-based polymer gel formulation and new formulation was named PAGATUG. The formulation which gives the nearest tissue elemental composition has been determined to be 3 % bis, 3 % AA, 5 % gelatine, 5 mM THPC, 0.01 mM HQ, 8.5 % glucose, and 3 % urea. The differences in electron density, number of electrons per gram and effective atomic number of PAGATUG gel were no more than 1, 0.5, and 0.8 % of the corresponding values for the soft tissue respectively. PAGATUG gels were irradiated by ⁶⁰Co radiotherapy unit photon beams with different doses and imaged using a 1.5T Siemens Avanto MRI scanner for different post irradiation times. In addition, the absorbance of the irradiated gels were evaluated using a double beam spectrophotometer. We found that the R ₂-sensitivity of polymer gel was improved by a factor of more than 2.6 in respect of the previously reported PAGAT polymer gel. Dose–absorbance sensitivity was obtained as 0.89 Au Gy^?1 and the results showed more stable response in respect of R ₂ investigation. An AUS-sensitivity of 107.7 Au nm Gy^?1 indicated to steep response variation. This read out parameter showed an acceptable linearity and dynamic dose range.     

Effects of pigments on the volume‐phase‐transition properties of N‐isopropylacrylamide gels as light‐modulation materials

The effects of pigments contained in N‐isopropylacrylamide (NIPAM) gels on their volume‐change properties were investigated. All the NIPAM gel particles, containing various kinds and concentrations of pigments, showed a volume phase transition at 34 °C. No pigment affected the volume‐phase‐transition temperature of the NIPAM gels. As the concentration of the pigment in the NIPAM gels was increased, the amount of the volume change of the NIPAM gels was reduced. The water absorptivity of the NIPAM gels in the swollen state decreased as the pigment concentration increased, whereas the water absorptivity in the shrunken state was almost constant. Reducing the initial monomer concentration of the polymerization of the NIPAM gel increased the water absorptivity in the swollen state. With an increase in the water absorptivity, the volume changes of the NIPAM gels containing pigments were increased. Prototype light modulators in which the NIPAM gel particles containing pigment were dispersed between glass plates were fabricated. The light modulator using the gel particles with improved diameter change (d/d₀ = 2.3, where d and d₀ are the equilibrium diameter and the diameter of the fully shrunken state at 50 °C, respectively) exhibited a larger transmittance change from 8 to 79% than that using the gel particles before the improvement (d/d₀ = 1.7; from 38 to 79%) according to temperature changes. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4644–4655, 2006     

The embedding of meta-tetra(hydroxyphenyl)-chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties

This study relates to nanoparticle (NP) platforms that attach to tumor cells externally and only deliver singlet oxygen for photodynamic therapy (PDT) while conserving the embedded photosensitizers (PS). As a model, we demonstrate the successful embedding of the PS meta‐tetra(hydroxyphenyl)‐chlorin (m‐THPC) in NP that are based on a sol–gel silica matrix and also show its positive effect on the singlet oxygen production. The embedding of m‐THPC inside silica NP is accomplished by a modified Stöber sol–gel process, in which (3‐aminopropyl)‐triethoxysilane is introduced during the reaction. Singlet oxygen delivery by the targetable photodynamic NP exceeds that from free PS molecules. In the physiological pH range, there is no significant pH‐induced decrease in the fluorescence of m‐THPC embedded in silica NP, which might otherwise affect the efficiency of PDT.     

Clinical Evaluation of the Cutaneous Phototoxicity of 5,10,15,20-Tetra (m-hydroxyphenyl)chlorin

The cutaneous phototoxic reaction induced by intravenous injection of 5,-10,-15,-20-tetra(m-hydroxyphenyl)chlorin (mTHPC) has been clinically evaluated in patients undergoing photodynamic therapy. These tests were performed on the backs of 23 patients with a solar simulator at various times after drug administration ranging from 5 h to 57 days. The mTHPC doses ranged from 0.1 to 0.3 mg/kg, and the illuminations lasted from 30 s up to 8 min. These tests have shown that the duration of the skin photosensitization induced after a typical therapeutic dose of mTHPC (0.15 mg/kg) is less important than with Photofrin®(2 mg/kg). The level of mTHPC in the skin was also assessed in vivo and at times corresponding to the irradiations using an optical fiber-based spectrofiuorometer. This study indicates that the light-induced fluorescence spectroscopy of mTHPC enables prediction of the degree of photosensitivity of the skin.     

On the Development of the VIPAR Polymer Gel Dosimeter for Three-Dimensional Dose Measurements

Summary: The new polymer gel dosimeter, based on the modification of the VIPAR gel composition, is described for the purpose of radiation dose distribution measurement in radiotherapy. It features increased concentration of the two VIPAR substrates: N-vinylpyrrolidone (8%) and gelatine (7.5%) (N,N′-methylenebisacrylamide was maintained at 4%), and the addition of copper sulphate (0.0008%) and ascorbic acid (0.007%) in order to facilitate the preparation through elimination of the need for deoxygenation of the gel. Following the exposure to ionizing radiation, polymerisation and cross-linking of the new gel monomers occurs retaining the spatial distribution of absorbed dose and causing opacity of the gel. Quantitative parameters of the new gel dose response were studied using magnetic resonance imaging to relate polymerisation induced physicochemical changes of the gel to dose. The dose threshold is found significantly lower than that of the original VIPAR gel. The linear part of measured spin-spin relaxation rate R₂(D) ( = 1/T₂(D)) reaches up to 35 Gy. Its slope and an intercept are slightly higher relative to the original VIPAR. The efficiency of the new polymer gel-magnetic resonance imaging dosimeter was also tested for dose verification of a 3D dose distribution planned by a commercially available treatment planning software (Eclipse External Beam v.6.5) and delivered by a 6 MV medical linear accelerator. The new polymer gel is proposed to be called, VIPAR^nd (after VIPAR-normoxic-double).     

A Comparison of the Photodynamic Effects of Temoporfin (mTHPC) and MC540 on Leukemia Cells: Efficacy and Apoptosis

The photodynamic effects of temoporfin (meso-tetrahy-droxyphenylchlorin, mTHPC) and merocyanine 540 (MC540) in murine myeloid leukemia M1 and WEHI 3B (JCS) cells were compared. The mTHPC was found to be more potent and selective. At a lethal dosage of 90% killing (LD90), only 1.3 μM of mTHPC and 4.2 kj/m2 of light irradiation was required, which was a 20-fold lower drug concentration and 11-fold smaller light dose than that required when using MC540. Meanwhile, three times less, or 15%, of the coincubated erythrocytes were destroyed by mTHPC than by MC540. Confocal micrographs showed that both drugs accumulated diffusely inside the cytoplasm in a very similar fashion, but mTHPC induced a more extensive apoptosis in photosensitized JCS cells. For example, at LD90, mTHPC practically killed all JCS cells via apoptosis and cleaved the DNA to extremely small 150 base-pair fragments. In contrast, among the JCS cells killed by MC540, about 88% died via apoptosis and large DNA fragments were abundant. Relative to MC540, the ability of mTHPC to trigger large-scale and thorough apoptosis in leukemia cells may help explain its potency and selectivity.     

Designing catechol‐end functionalized poly(DMAm‐co‐NIPAM) by RAFT with tunable LCSTs

Providing catechol‐end functionality to controlled structure lower critical solution temperature (LCST) copolymers is attractive, given the versatility of catechol chemistry for tethering to nanostructures. Controlled polymer chain lengths with catechol RAFT end groups are of interest to provide tunable LCST behavior to nanoparticles, although these polymerizations are relatively unexplored. Herein, the reactivity ratios for the RAFT copolymerization of N,N‐dimethylacrylamide (DMAm) and N‐isopropylacrylamide (NIPAM) pairs based on catechol‐end RAFT agents using an in situ NMR technique were first determined. Several catechol‐end poly(DMAm‐co‐NIPAM) samples were then prepared using the RAFT agent to provide copolymer. The reactivity ratios for the DMAm‐NIPAM pair were r_DMAm = 1.28–1.31 and r_NIPAM = 0.48–0.51. All the poly(DMAm‐co‐NIPAM) samples were found to have M_n values ≤ 26 kDa and Ð < 1.08 with LCST values ranging from 31 to 92°C, while maintaining a short range of glass transition temperature (T_g = 118–137°C). The difference in LCST values for the catechol functionalized poly(DMAm‐co‐NIPAM) based on 0.5 wt% aqueous buffered solutions at pH 5.5 and 8.5 was found to be <3.0°C. These conditions are suitable for subsequent catechol‐induced coordination and nucleophilic addition chemistry for covalent and noncovalent linkages during subsequent post‐modification. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 4062–4070     

Structural parameters of polyacrylamide hydrogels obtained by the Equilibrium Swelling Theory

In this paper, the synthesis and structural characterization of a series of polyacrylamide hydrogels with different degrees of reticulation are reported. Although the Equilibrium Swelling Theory was recognized as a simple and reliable tool for the determination of structural hydrogels network parameters like equilibrium degree of swelling, cross-link ratio and mesh size, this is the first application of this methodology for polyacrylamide hydrogels. By changing the total monomer content in the synthesis solution (%T) from 5 to 30%, at a fixed value of cross-linker content in the total monomer amount (%C) of 5%, the final parameter obtained, the mesh size, can be tuned from 2 to 0.3 nm. It was also possible to change the mesh size (0.19-0.35) by varying %C from 5 to 12% (at %T = 20%). Scanning Electron Microscopy images for the most different formulations are shown and corroborate data obtained from the theory.     

Rhodamine-conjugated acrylamide polymers exhibiting selective fluorescence enhancement at specific temperature ranges

A simple copolymer, poly(NIPAM-co-RD), consisting of N-isopropylacrylamide (NIPAM) and rhodamine (RD) units, behaves as a fluorescent temperature sensor exhibiting selective fluorescence enhancement at a specific temperature range (25–40 °C) in water. This is driven by a heat-induced phase transition of the polymer from coil to globule. At low temperature, the polymer exists as a polar coil state and shows very weak fluorescence. At >25 °C, the polymer weakly aggregates and forms a less polar domain within the polymer, leading to fluorescence enhancement. However, at >33 °C, strong polymer aggregation leads to a formation of huge polymer particles, which suppresses the incident light absorption by the RD units and shows very weak fluorescence. In the present work, effects of polymer concentration and type of acrylamide unit in the polymer have been investigated. The increase in the polymer concentration in water leads to a formation of less polar domain even at low temperature and, hence, widens the detectable temperature range to lower temperature. Addition of N-n-propylacrylamide (NNPAM) or N-isopropylmethacrylamide (NIPMAM) component to the polymer, which has lower or higher phase transition temperature than that of NIPAM, enables the aggregation temperature of the polymer to shift. This then shifts the detectable temperature region to lower or higher temperature.