Aqueous-ethanol nitro blue tetrazolium solutions for high dose dosimetry

The ions of nitro blue tetrazolium (NBT²⁺) in aqueous ethanol solution are readily reduced radiolytically first to monoformazan (MF⁺) and then to diformazan (DF) having high linear molar extinction coefficients at the absorption maxima of 522 and 570–610 nm. Spectrophotometric analysis then provides potential use in high-dose dosimetry over the dose ranges of 0.1–1 and 1–30 kGy. The solution is stable for the first 24 h after the irradiation.     

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.     

Variation in dose response of three dosimetry systems based on diphenyl thiocarbazone

Journal of Radioanalytical and Nuclear Chemistry - Three different dosimetry systems were prepared based on diphenyl thiocarbazone (DTH) dye: polymer films made with, poly(vinyl alcohol), DTH...     

Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer

In current clinical practice, photodynamic therapy (PDT) is carried out with prescribed drug doses and light doses as well as fixed drug-light intervals and illumination fluence rates. This approach can result in undesirable treatment outcomes of either overtreatment or undertreatment because of biological variations between different lesions and patients. In this study, we explore the possibility of improving PDT dosimetry by monitoring drug photobleaching and photoproduct formation. The study involved 60 mice receiving the same drug dose of a novel verteporfin-like photosensitizer, QLT0074, at 0.3 mg/kg body weight, followed by different light doses of 5, 10, 20, 30, 40 or 50 J/cm2 at 686 nm and a fluence rate of 70 mW/cm2. Photobleaching and photoproduct formation were measured simultaneously, using fluorescence spectroscopy. A ratio technique for data processing was introduced to reliably detect the photoproduct formed by PDT on mouse skin in vivo. The study showed that the QLT0074 photoproduct is stable and can be reliably quantified. Three new parameters, photoproduct score (PPS), photobleaching score (PBS) and percentage photobleaching score (PBS%), were introduced and tested together with the conventional dosimetry parameter, light dose, for performance on predicting PDT-induced outcome, skin necrosis. The statistical analysis of experimental results was performed with an ordinal logistic regression model. We demonstrated that both PPS and PBS improved the prediction of skin necrosis dramatically compared to light dose. PPS was identified as the best single parameter for predicting the PDT outcome.     

Reduced dose uncertainty in MRI-based polymer gel dosimetry using parallel RF transmission with multiple RF sources

In this work, we present the feasibility of using a parallel RF transmit with multiple RF sources imaging method (MultiTransmit imaging) in polymer gel dosimetry. Image quality and B₁ field homogeneity was statistically better in the MultiTransmit imaging method than in conventional single source RF transmission imaging method. In particular, the standard uncertainty of R ₂ was lower on the MultiTransmit images than on the conventional images. Furthermore, the MultiTransmit measurement showed improved dose resolution. Improved image quality and B₁ homogeneity results in reduced dose uncertainty, thereby suggesting the feasibility of MultiTransmit MR imaging in gel dosimetry.     

Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy

Experimental therapies for Barrett's esophagus, such as 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), aim to ablate the premalignant Barrett's epithelium. However, the reproducibility of the effects should be improved to optimize treatment. Accurate irradiation with light of a proper wavelength (633 nm), fluence and fluence rate has shown to be critical for successful ALA-PDT. Here, we have used in situ light dosimetry to adjust the fluence rate measured within the esophagus for individual animals and monitored protoporphyrin IX (PpIX) fluorescence photobleaching simultaneously. Rats were administered 200 mg kg-1 ALA (n = 14) or served as control (n = 7). Animals were irradiated with an in situ measured fluence rate of 75 mW cm-2 and a fluence of 54 J cm-2. However, this more accurate method of light dosimetry did not decrease the variation in tissue response. Large differences were also observed in the dynamics of PpIX fluorescence photobleaching in animals that received the same measured illumination parameters. We found that higher PpIX fluorescence photobleaching rates corresponded with more epithelial damage, whereas lower rates corresponded with no response. A two-phased decay in PpIX fluorescence could be identified in the response group, with a rapid initial phase followed by a slower rate of photobleaching. Non-responders did not show the rapid initial decay and had a significantly lower rate of photobleaching during the second phase of the decay (P = 0.012).     

The features of electron dose distributions in circular objects: Comparison of Monte Carlo calculation predictions with dosimetry

The features of electron dose field formation in the multi-layer circular objects are related with its surface irregularity such as convexity, concavity and roundness of inner and outer layers. The simulation of dose distributions in multi-layer tubes irradiated with a scanned electron beam (EB) was carried out by Monte Carlo (MC) method with utilization of the software ModeCEB. The effects of mutual influence on dose field formation in contacting multi-layers tubes irradiated with EB were MC simulated and measured with a film dosimetry. An experimental validation of the obtained simulation predictions for dose distributions in multi-layer tubes irradiated with 10 MeV electrons was performed on radiation facility with linear electron accelerator LAE 13/9, INCT, Warsaw. Comparison of MC simulation results with a film dosimetry is discussed in the report.     

Uncertainty estimation in Co gamma-ray dosimetry at JAERI involving a two-way dose intercomparison study with NPL in the dose range 1–50 kGy

The uncertainties in ⁶⁰Co gamma-ray dosimetry at JAERI have been estimated by reviewing irradiation and calibration procedures. The uncertainty in dose delivered by the JAERI calibration system has been estimated to be 2.2% (2σ) and the uncertainty in dose measurement using JAERI alanine/ESR transfer dosimeters has been estimated to be 3.4% (2σ). A two-way dose intercomparison study between NPL and JAERI employing alanine-PS, alanine-paraffin, and dichromate dosimeters as transfer dosimeters was performed to confirm the estimated uncertainty over the dose range 1–50 kGy. Dose intercomparison results using both alanine and dichromate dosimeters show agreement within about 2%, which gives confidence in the estimated uncertainty in ⁶⁰Co gamma-ray dosimetry at JAERI.     

Pharmacokinetics of a tri-glucoconjugated 5,10,15-(meta)-trihydroxyphenyl-20-phenyl porphyrin photosensitizer for PDT. A single dose study in the rat

Photodynamic therapy (PDT) involves a non invasive treatment of small and superficial cancers using a photosensitive drug and light to kill tumoral cells. 5,10,15-meso-tri-(meta-O-beta-D-glucosyloxyphenyl)-20-phenylporphyrin [m-TPP(glu)3] is a new photosensitizer (PS) with more enhanced photocytotoxicity relative to 5,10,15,20-meso-tetra-(meta-hydroxyphenyl) chlorin [m-THPC] (Foscan). It was injected intravenously once to healthy rats at three different doses (0.25, 0.5 and 1 mg kg(-1)) and compared to m-THPC (0.3 mg kg(-1)). Pharmacokinetic parameters for both photosensitizers were derived from plasma concentration-time data using a non-compartmental analysis and a two-compartment pharmacokinetic model. m-TPP(glu)3 is more rapidly eliminated throughout the organism than m-THPC. Its mean plasma clearance is 19 mL h(-1) kg(-1) (6 mL h(-1) kg(-1) for m-THPC), and its mean residence time is 5h (20 h for m-THPC). The area under curve (AUC) and initial mean serum concentration (C0) were found to be proportional to the dose. As for Foscan, no metabolite of m-TPP(glu)3 was detected in plasma. The biodistribution study demonstrates that the most significant amount of m-TPP(glu)3 was concentrated in organs such as lung, liver and spleen which are rich in reticulo-endothelial cells. Maximum concentrations were reached in organs 14 h after IV administration. At 48 h, the photosensitizer was essentially eliminated from all organs. Because of its shorter elimination time, m-TPP(glu)3 is more attractive than m-THPC as a PDT agent since secondary side effects of shorter duration could be expected.     

Medical dosimetry in Hungary

Radiation exposure of medical staff during cardiological and radiological procedures was investigated. The exposure of medical staff is directly connected to patient exposure. The aim of this study was to determine the distribution of doses on uncovered part of body of medical staff using LiF thermoluminescent (TL) dosimeters in seven locations.Individual Kodak film dosimeters (as authorized dosimetry system) were used for the assessment of medical staff's effective dose. Results achieved on dose distribution measurements confirm that wearing only one film badge under the lead apron does not provide enough information on the personal dose.The value of estimated annual doses on eye lens and extremities (fingers) were in good correlation with international publications.     

The Yin and Yang of PDT and PTT

In Chinese philosophy, yin and yang ("dark-bright," "negative-positive") describe how seemingly opposite or contrary forces may actually be complementary, interconnected and interdependent. This paper provides this perspective on photodynamic and photothermal therapies, with a focus on the treatment of solid tumors. The relative strengths and weaknesses of each modality, both current and emerging, are considered with respect to the underlying biophysics, the required technologies, the biological effects, their translation into clinical practice and the realized or potential clinical outcomes. For each specific clinical application, one or the other modality may be clearly preferred, or both are effectively equivalent in terms of the various scientific/technological/practical/clinical trade-offs involved. Alternatively, a combination may the best approach. Such combined approaches may be facilitated by the use of multifunctional nanoparticles. It is important to understand the many factors that go into the selection of the optimal approach and the objective of this paper is to provide guidance on this.     

Photodynamic therapy of vertebral metastases: evaluating tumor-to-neural tissue uptake of BPD-MA and ALA-PpIX in a murine model of metastatic human breast carcinoma

Photodynamic therapy has been successfully applied to numerous cancers. Its potential to treat cancer metastases in the spine has been demonstrated previously in a preclinical animal model. The aim of this study was to test two photosensitizers, benzoporphyrin-derivative monoacid ring A (BPD-MA) and by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), for their potential use to treat bony metastases. The difference in photosensitizer concentration in the spinal cord and the surrounding tumor-bearing vertebrae was of particular interest to assess the risk of potential collateral damage to the spinal cord. Vertebral metastases in a rat model were generated by intracardiac injection of human breast cancer cells. When tumor growth was confirmed, photosensitizers were injected systemically and the animals were euthanized at different time points. The following tissues were harvested: liver, kidney, ovaries, appendicular bone, spinal cord and lumbar vertebrae. Photosensitizer tissue concentration of BPD-MA or PpIX was determined by fluorescence spectrophotometry. In contrast to BPD-MA, ALA-PpIX did not demonstrate an appreciable difference in the uptake ratio in tumor-bearing vertebrae compared to spinal cord. The highest ratio for BPD-MA concentration was found 15 min after injection, which can be recommended for therapy in this model.     

Use of bubble detectors in personal neutron dosimetry

ICRP 60 recommendation require to improve the lowest limit of detection (LLD) of an individual neutron dosimeter by a factor estimated up to about five. Bubble neutron detectors could fulfill such conditions, the LLD of systems already available is claimed to be well below 10 Sv. We have tried to test them at different neutron sources. The results obtained are presented.Work partially supported through EC Project F13P-CT93-0072.     

Evaluation of photodynamic therapy (PDT) procedures using microfluidic system

A hybrid PDMS/glass microfluidic system for evaluation of the efficiency of photodynamic therapy is presented. 5-aminolevulinic acid (ALA) was used as a precursor of photosensitizer. The geometry of the microdevice presented in this paper enables to test different concentrations of the photosensitizer in a single assay. The viability of the A549 cells was determined 24 h after PDT procedure (irradiation with light which induced a photosensitizer accumulated in carcinoma cells, λ = 625 nm). The presented results confirmed the possibility to perform the photodynamic therapy process in vitro in microscale and the possibility to assess its effectiveness. Moreover, because two identical microstructures on a single chip were performed, the microchip can be used for examination simultaneously various cell lines (carcinoma and normal) or various photosensitizers.     

Proton dosimetry in the radiation chemistry of ionic salts

Layers of thickness less than the range are used in conjunction with the known flux density. The energy loss may be calculated or may be measured from the yield per particle for specimens of several thicknesses.     

Fluence Rate Determines PDT Efficiency in Breast Cancer Cells Displaying Different GSH Levels

Photodynamic therapy (PDT) appears as a promising alternative in the treatment of breast cancer since it can be highly effective in curing cancer while preserving normal tissue. However, predicting outcomes in PDT still constitutes a great challenge. One of the parameters that are usually empirically determined is the rate of photon flux delivered to the tissue (light fluence rate). In the present study, we intended to understand why monolayers of human cells derived from mammary adenocarcinomas (MDA-MB-231 and MCF-7) respond quite differently to fluence rates (cells were irradiated either for 6 or for 16 min) at a fixed light dose (4.5 J cm⁻²) delivered with an array of LEDs in a typical methylene blue PDT protocol. While death rates of MDA-MB-231 cells were insensitive to the fluence rate, MCF-7 cells showed a quite impressive (three times) decrease in cell death levels in the shorter irradiation protocol. Independent on cell type cell death was invariably correlated with the depletion of reduced glutathione intracellular levels and consequently with widespread redox misbalance. Our data show the potential to optimize fluence rates to provide exhaustion of the cell antioxidant responses in order to circumvent therapy resistance of breast tumors.     

Study on dosimetry of bremsstrahlung radiation processing

The dosimetry in high-power bremsstrahlung irradiation for the industrial processing has been studied. The dosimeter systems used are cylindrical ionization chamber to measure average exposure rate and CTA, clear PMMA and alanine dosimeters for routine dosimetry. The results gave some useful information on the measurement of average exposure rate using the ionization chamber. Clear PMMA and alanine dosimeters showed good characteristics for their usefulness as routine dosimeters for X-ray irradiation in the industrial processing.     

On the possibility of using organic phosphors in thermoluminescence dosimetry

Organic materials in general and polymers in particular have traditionally been considered as to be phosphors and have been ruled out as materials which could be useful in dosimetry of ionizing radiations by thermoluminescence. Some results reported during the past decade suggested possibilities of organic phosphors with good thermoluminescence characteristics. Experiments were undertaken to exploit the various possibilities. The results show that “crystalline polymers” can have adequate thermoluminescence properties to be useful in dosimetry. It is suggested that further studies on thermoluminesence in crystalline polymers and highly drawn fibers of high polymers will prove fruitful.     

Long-lived contaminants in cyclotron-produced radiopharmaceuticals: measurement and dosimetry

Oxygenated target waters of cyclotron targets contain long-lived contaminants due to (p,n) reactions in the HAVAR target window that are spalled into the target water. These contaminants are largely removed during the synthesis of the final imaging agent. Currently the USP requires that the final drug product be 99.5% pure, so the total activity of the long-lived contaminants can be no more than 0.5% of the final radiopharmaceutical product. A method has been developed to identify and quantify the primary contaminants using high resolution gamma spectroscopy and VRF, a new spectrum analysis tool. Uptake, retention, and excretion functions for each of the contaminating isotopes in a soluble, injected chemical form have also been calculated using International Commission on Radiological Protection (ICRP) Publication 123 models and are presented in the Appendices A and B of Electronic Supplementary Material. In addition, specific organ and effective dose coefficients were also calculated using ICRP Publication 103 tissue weighting factors and are also presented in the Appendices A and B of Electronic Supplementary Material. Typical imaging agents have contaminant loads far below the USP limit and contribute negligible doses to the patients receiving the drugs.