Kazuyuki Hosokawa

The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry.

Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.

Technical Note: Preliminary investigations into the use of a functionalised polymer to reduce diffusion in Fricke gel dosimeters

PURPOSE A modification of the existing PVA-FX hydrogel has been made to investigate the use of a functionalised polymer in a Fricke gel dosimetry system to decrease Fe(3+) diffusion. METHODS The chelating agent, xylenol orange, was chemically bonded to the gelling agent, polyvinyl alcohol (PVA) to create xylenol orange functionalised PVA (XO-PVA). A gel was created from the XO-PVA (20% w/v) with ferrous sulfate (0.4 mM) and sulfuric acid (50 mM). RESULTS This resulted in an optical density dose sensitivity of 0.014 Gy(-1), an auto-oxidation rate of 0.0005 h(-1), and a diffusion rate of 0.129 mm(2) h(-1); an 8% reduction compared to the original PVA-FX gel, which in practical terms adds approximately 1 h to the time span between irradiation and accurate read-out. CONCLUSIONS Because this initial method of chemically bonding xylenol orange to polyvinyl alcohol has inherently low conversion, the improvement on existing gel systems is minimal when compared to the drawbacks. More efficient methods of functionalising polyvinyl alcohol with xylenol orange must be developed for this system to gain clinical relevance.

A reduction of diffusion in PVA Fricke hydrogels

A modification to the PVA-FX hydrogel whereby the chelating agent, xylenol orange, was partially bonded to the gelling agent, poly-vinyl alcohol, resulted in an 8% reduction in the post irradiation Fe3+ diffusion, adding approximately 1 hour to the useful timespan between irradiation and readout. This xylenol orange functionalised poly-vinyl alcohol hydrogel had an OD dose sensitivity of 0.014 Gy−1 and a diffusion rate of 0.133 mm2 h−1. As this partial bond yields only incremental improvement, it is proposed that more efficient methods of bonding xylenol orange to poly-vinyl alcohol be investigated to further reduce the diffusion in Fricke gels.

Technical Note: Dose distributions in the vicinity of high‐density implants using 3D gel dosimeters

Purpose In this work, we develop a methodology for using Fricke gel dosimeters for dose distribution measurements surrounding high‐density implants which circumvents artifact production by removing the obstruction during imaging. Methods Custom 3D printed molds were used to set cavities in Fricke gel phantoms to allow for the suspension of high‐density implants in different geometries. This allowed for the metal valve extracted from a temporary tissue expander to be suspended during irradiation, and removed during optical‐CT scanning. Results The removal of the metal implant and subsequent backfilling of the remaining cavity with optically matched fluid prior to dose evaluation enables accurate optical‐CT scanning of the gel dosimeters. Results have shown very good agreement between measured and calculated doses within 2 mm from the surface of the implant. Slight deviations are present within 1 mm of the interface. Conclusions Artifacts in the form of radial streaking, cold spots, and hot spots were all reduced using this technique, enabling the broader and more accurate use of optical‐CT for the imaging of gels containing opaque objects.