Synchrotron stereotactic radiotherapy: dosimetry by Fricke gel and Monte Carlo simulations

Synchrotron stereotactic radiotherapy (SSR) consists in loading the tumour with a high atomic number element (Z), and exposing it to monochromatic x-rays from a synchrotron source (50-100 keV), in stereotactic conditions. The dose distribution results from both the stereotactic monochromatic x-ray irradiation and the presence of the high Z element. The purpose of this preliminary study was to evaluate the two-dimensional dose distribution resulting solely from the irradiation geometry, using Monte Carlo simulations and a Fricke gel dosimeter. The verification of a Monte Carlo-based dosimetry was first assessed by depth dose measurements in a water tank. We thereafter used a Fricke dosimeter to compareMonteCarlo simulations with dosemeasurements. The Fricke dosimeter is a solution containing ferrous ions which are oxidized to ferric ions under ionizing radiation, proportionally to the absorbed dose. A cylindrical phantom filled with Fricke gel was irradiated in stereotactic conditions over several slices with a continuous beam (beam section = 0.1 × 1 cm2). The phantom and calibration vessels were then imaged by nuclear magnetic resonance. The measured doses were fairly consistent with those predicted by Monte Carlo simulations. However, the measured maximum absolute dose was 10% underestimated regarding calculation. The loss of information in the higher region of dose is explained by the diffusion of ferric ions. Monte Carlo simulation is the most accurate tool for dosimetry including complex geometries made of heterogeneous materials. Although the technique requires improvements, gel dosimetry remains an essential tool for the experimental verification of dose distribution in SSR with millimetre precision

Normoxic polyacrylamide gel doped with iodine: Response versus X-ray energy

The basis of Synchrotron Stereotactic Radio-Therapy (SSRT) is the incorporation of high atomic number atoms (iodine, for example) into the tumour mass followed by an irradiation with a monochromatic, low energy, X-ray beam from a synchrotron source. The purpose of the present study was to determine whether polymer gel dosimetry could be used to measure the enhancement of absorbed energy induced by the iodine in the media. We have used a standard nPAG formulation, loaded with NaI and the irradiations were performed either with monochromatic X-rays at the ESRF medical beamline or with a conventional 6MV X-ray beam from a linear accelerator at the Grenoble University Hospital.We observed sensitivity increase with iodine loaded gels irradiated at low energies, in good agreement with the theoretical iodine dose-enhancement. As expected, the response of the iodine-doped polymer gel was not increased after irradiation with mega-voltage X-rays.We demonstrate in this study that polymer gel dosimeters can be used for measuring dose-enhancement due to iodine presence in SSR treatment

In vivo measurement of gadolinium concentration in a rat glioma model by monochromatic quantitative computed tomography: comparison between gadopentetate dimeglumine and gadobutrol

Rationale and Objectives: Monochromatic quantitative computed tomography allows a nondestructive and quantitative measurement of gadolinium (Gd) concentration. This technique was used in the C6 rat glioma model to compare gadopentetate dimeglumine and gadobutrol. Methods: Rats bearing late-stage gliomas received 2.5 mmol/kg (392.5 mg Gd/kg) of gadopentetate dimeglumine (n 5) and gadobutrol (n 6) intravenously before the imaging session performed at the European Synchrotron Radiation Facility. Results: Monochromatic quantitative computed tomography enabled in vivo follow-up of Gd concentration as a function of time in specified regions of interest. Surprisingly, after gadobutrol injection, Gd concentrations in the center and periphery of the tumor were higher than those after gadopentetate injection, although identical in normal and contralateral area of the brain. Conclusion: The in vivo assessment of absolute Gd concentrations revealed differences in gadobutrol and gadopentetate dimeglumine behaviors in tumoral tissues despite injections in the same conditions. These differences might be attributed to different characteristics of the contrast agents

Fast dose calculation for stereotactic synchrotron radiotherapy

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Absolute cerebral blood volume and blood flow measurements based on synchrotron radiation quantitative computed tomography

Synchrotron radiation computed tomography opens new fields by using monochromatic x-ray beams. This technique allows one to measure in vivo absolute contrast-agent concentrations with high accuracy and precision, and absolute cerebral blood volume or flow can be derived from these measurements using tracer kinetic methods. The authors injected an intravenous bolus of an iodinated contrast agent in healthy rats, and acquired computed tomography images to follow the temporal evolution of the contrast material in the blood circulation. The first image acquired before iodine infusion was subtracted from the others to obtain computed tomography slices expressed in absolute iodine concentrations. Cerebral blood volume and cerebral blood flow maps were obtained after correction for partial volume effects. Mean cerebral blood volume and flow values (n 7) were 2.1 ± 0.38 mL/100 g and 129 ± 18 mL · 100 g−1 · min−1 in the parietal cortex; and 1.92 ± 0.32 mL/100 g and 125 ± 17 mL · 100 g−1 · min−1 in the caudate putamen, respectively. Synchrotron radiation computed tomography has the potential to assess these two brainperfusion parameters. Key Words: Synchrotron radiation— Computed tomography—Cerebral blood volume—Cerebral blood flow—Iodinated contrast agent—Partial volume effects

Sensitivity variation of doped Fricke gel irradiated with monochromatic synchrotron X-rays between 33.5 and 80 keV

An experimental binary radiotherapy proposes the concomitant use of a high-Z compound and synchrotron X rays for enhancing radiation dose selectively in tumours by a photoelectric effect. This study aimed at measuring the resulting dose enhancement in irradiated material. A doped Fricke gel dosemeter model was manufactured with 10 mg ml1 of iodine (Telebrix) or barium (Micropaque). Samples were irradiated with a monochromatic synchrotron beam at 33.5, 50, 65 and 80 keV. The ensuing enhancement of the sensitivity of the dosemeter was derived from the nuclear magnetic resonance relaxation rates measured at different X-ray doses. Our results demonstrate (1) the preservation of a linear relationship between relaxation rates and X-ray doses for dosemeters doped with high-Z atoms and (2) a clear energy-dependent sensitivity enhancement for barium-doped Fricke gels. This enhancement was neither reproducible with iodinated compounds nor clearly related to the expected dose enhancement factor. However 1% barium sulphate in the gel could significantly improve the gel\u27s response when it was irradiated by low-energy X rays

Preparation, Biodistribution and Neurotoxicity of Liposomal Cisplatin following Convection Enhanced Delivery in Normal and F98 Glioma Bearing Rats

The purpose of this study was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment of the F98 rat glioma. The first was a commercially produced agent, Lipoplatin TM, which currently is in a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC). The second, produced in our laboratory, was based on the ability of cisplatin to form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS). The in vitro tumoricidal activity of the former previously has been described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency of 25 % and showed more potent in vitro cytotoxicity against F98 glioma cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention at 24 h after intracerebral (i.c.) convection enhanced delivery (CED) to F98 glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor bearing Fischer rats following i.c. CED of Lipoplatin TM or CHEMS liposomes or their ‘‘hollow’ ’ counterparts. Unexpectedly, Lipoplatin TM was highly neurotoxic when given i.c. by CED and resulted in death immediately following or within a few days after administration. Similarly ‘‘hollow’’ Lipoplatin TM liposomes showed similar neurotoxicity indicating that this was due to the liposomes themselves rather than the cisplatin. This was particularly surprising since Lipoplatin TM has been well tolerated when administered intravenously. In contrast, CHEMS liposomes and their ‘‘hollow’ ’ counterparts were clinically well tolerated. However, a variety of dos

Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways

Combination of cis-platinum with ionizing radiation is one of the most promising anticancer treatments that appears to be more efficient than radiotherapy alone. Unlike conventional X-ray emitters, accelerators of high energy particles like synchrotrons display powerful and monochromatizable radiation that makes the induction of an Auger electron cascade in cis-platinum molecules [also called photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we examined the molecular consequences of one of the first attempts of synchrotron PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble-France). PATPlat was found to result in an extra number of slowly repairable DNA double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and activation of proto-oncogenic c-Abl tyrosine kinase

Coronary angiography with synchrotron X-ray source on pigs after iodine or gadolinium intravenous injection

Arterial angiography, an invasive method for the diagnosis of vascular alterations, is a standard procedure established many years ago. The technique provides excellent images of the coronary arteries and their anatomic configuration but is not suitable for general screening or repetitive controls in clinical research due to the use of intra-arterial catheters. As alternatives, noninvasive methods such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US) have been continuously improving during the recent years, but they still provide less relevant images (1- 4). Another approach, usually known as K-edge digital subtraction angiography, uses monochromatic x-rays from synchrotron sources (5). After intravenous (IV) injection of the contrast agent, two images are produced with monochromatic beams, above and below the contrast agent K-edge (iodine or gadolinium). The logarithmic subtraction of the two measurements results in an iodine- or gadolinium- enhanced image, which can be precisely quantified. The aim is to provide a less invasive technique than the conventional imaging procedure to follow patients after coronary interventions. First in vivo studies have been performed on pigs at the European Synchrotron Radiation Facility (ESRF) to test th