John Kalef-Ezra

Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma

The purpose of this study is to test the hypothesis that gold nanoparticle (AuNP, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNP-mediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective at 42 Gy than at 30 Gy (both at 68 keV median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose ( approximately 42 Gy), 68 keV was more effective than 157 keV. Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 50%) and increasing long-term survivals. It is concluded that gold nanoparticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.

Radiation burden of patients undergoing endovascular abdominal aortic aneurysm repair

INTRODUCTION Endovascular repair of abdominal aortic aneurysm (EVAR) requires the patients extended exposure to x-rays, before, during, and after the intervention. The aim of this study was to determine the radiation exposure of patients undergoing EVAR and to assess the probability for the induction of both late and early radiation-related effects. METHODS During the period of May 2006 to December 2007 EVAR was carried out in 62 patients using a mobile C-arm unit. The following dosimetric quantities were assessed: fluoroscopy time, cumulative dose in air, dose-area product, field area, and peak skin dose. RESULTS The duration of fluoroscopy and the body mass index were found to be the main factors that influence the radiation burden in our hospital. The mean effective dose per procedure, 6.2 mSv, was between that from a planar coronary angiography and a coronary angioplasty. Taking into account the computed tomography (CT) procedure-related angiographies carried out during the first year, patients receive a total effective dose of about 62 mSv within the first year. In vivo dosimetry showed that the peak skin dose was linearly correlated with cumulative dose in air and did not exceed 1.0 Gy, ie, it was less than the threshold for any acute skin reaction. CONCLUSION Repair of abdominal aortic aneurysm results in substantial radiation burden. Radiation-related risks for carcinogenesis and skin injuries are factors that have to be taken into account in the selection of the strategy of each facility.

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25-75 micron-wide microplanar beams separated by wider (100-400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.

Body Composition in Ambulatory Patients With Multiple Sclerosis

The aim of this study was to compare between ambulatory patients with multiple sclerosis (MS) and control subjects, bone mineral density (BMD), and body composition, that is, percent of bone minerals (M%), fat (F%), and remaining substances (L%). Total body composition and BMD were measured by dual-energy X-ray absorptiometry in 68 patients with definite MS and Expanded Disability Status Scale (EDSS) score ≤ 6.5 (41 females and 27 males) and 114 control individuals (72 females and 42 males). The amount of F%, L%, M%, and BMD in the whole body, arms, and trunk was not statistically different between MS patients (males and females) and controls, except in the lower extremities of female patients where there was increased F% and reduced L% compared with controls. There were no correlations between F%, L%, M%, and BMD at any anatomic region with EDSS or the cumulative corticosteroid dose. The reduced L% in the lower extremities of female patients suggests a possible increased subsequent risk of osteoporosis in the legs. Brief steroid courses administered during disease exacerbations in ambulatory MS patients did not result in obvious adverse consequences.

Epithermal beam development at the BMRR: dosimetric evaluation.

The utilization of an epithermal-neutron beam for neutron capture therapy (NCT) is desirable because of the increased tissue penetration relative to a thermal-neutron beam. Over the past few years, modifications have been and continue to be made at the Brookhaven Medical Research Reactor (BMRR) to produce an optimal epithermal beam by changing filter components. An optimal incident epithermal beam should contain the minimum possible fast-neutron component and no thermal neutrons. Recently, a new moderator for the epithenmal beam was installed at the epithermal port of the BMRR. With the installation of this moderator, an optimal beam has been realized [1]. This new moderator is a combination of alumina (Al2O3) bricks and aluminum (Al) plates. A 0.51-mm thick cadmium (Cd) sheet has reduced the thermal-neutron intensity drastically. Furthermore, an 11.5-cm thick bismuth (Bi) plate installed at the port surface has reduced the gamma-dose component to negligible levels. In order to compare various filter configurations for best optimization [2], the following parameters have been measured on the beam axis, directly in front of the epithermal port: 1) Thermal-neutron fluence rate free in air 2) Epithermal-neutron fluence rate free in air 3) Fast-neutron fluence rate free in air 4) Thermal-neutron fluence rate in a polyethylene cylindrical head phantom as a function of distance along the axis of the phantom 5) Fast-neutron dose rate in soft tissue, free in air, and 6) Gamma-dose rate in soft tissue, free in air.

Electron density of tissues and breast cancer radiotherapy: a quantitative CT study

PURPOSE To obtain more accurate data on the electron density of tissues to be used in the treatment planning of breast cancer patients. METHODS AND MATERIALS Single kVp quantitative computed tomography was applied in 70 women, 20 to 77 years old, to study the electron density of the breast, the thoracic wall close and parallel to the breast, and the lung parenchyma. RESULTS The electron density of the entire breast decreases with increasing age in premenopausal women and remains practically constant in postmenopausal women (8% less than that of water). No difference was found in the electron densities of the right and left breast. The electron density of the lung parenchyma in proximity to the breast is lower than the density in the entire lung parenchyma. CONCLUSIONS Whenever no accurate data is available on individual patients, the electron density values to be used in treatment planning for breast and thoracic wall have to take into account both age and menstrual status. The regional differences in electron density of the lung also have to be considered.

A Beam-Modification Assembly for Experimental Neutron Capture Therapy of Brain Tumors

Recent attempts to treat intracerebral rat gliomas by boron neutron capture therapy (BNCT) have been somewhat disappointing [1,2], perhaps in part because of excessive whole-body and nasopharyngeal irradiation. Intracerebral rat gliomas were treated by BNCT with more success using a new beam-modification assembly (Figure 1). Rats were infused with the sulfhydryl borane dimer Na4 10B24H22S2 intraperitoneally before irradiation at the rate of ~2 mg 10B per kg body weight per hour for 72 hours [3]. Boron-10 concentrations measured by the neutron-induced prompt-gamma technique [4] in 0.3 ml aliquots of blood sampled from each rat several minutes after the end of infusion averaged 35 μg per gram (range 24–42 μg/g). Boron-10 concentrations in similar rat brain tumors after 72 hours of identical infusion were twenty-five percent lower than blood 10B concentrations, on the average.

Renal cell carcinoma: value of multiphase MDCT with multiplanar reformations in the detection of pseudocapsule.

OBJECTIVE The purpose of this study was to assess the diagnostic performance of four-phase (unenhanced, arterial, portal, and nephrographic-excretory) MDCT with multiplanar reformations in the detection of pseudocapsule of renal cell carcinoma (RCC). MATERIALS AND METHODS In a retrospective study of 29 histologically proven RCCs in 29 patients (17 men, 12 women; mean age, 59 years), examinations were performed with a 16-MDCT scanner. The protocol included unenhanced and three-phase (arterial, portal, and nephrographic-excretory) contrast-enhanced CT. The data were analyzed by two reviewers blinded to the histopathologic results. Any discrepancy was resolved by consensus. The presence of a regular, high- or low-attenuation halo surrounding a renal neoplasm was considered to represent renal pseudocapsule. The accuracy of MDCT in the detection of pseudocapsule with the histopathologic results as the standard of reference was evaluated. Unenhanced transverse images and multiplanar reformations in the transverse, coronal, and sagittal planes of each contrast-enhanced phase were separately analyzed. The chi-square two-way test was used to compare each CT phase and multiplanar reformation with histologic results. RESULTS The mean diameter of RCCs on CT scans was 5.6 cm (range, 2.8-15 cm), in accordance with the pathologic result. MDCT enabled detection of renal pseudocapsule in 20 of 29 RCCs with 83% sensitivity, 80% specificity, 95% positive predictive value, 50% negative predictive value, and 83% overall accuracy. Imaging in the portal and nephrographic phases with coronal and sagittal reformations proved more accurate in the detection of pseudocapsule (p < 0.05). CONCLUSION Multiphase MDCT with multiplanar reformations had satisfactory results in the detection of renal pseudocapsule in RCC.

External beam irradiation in angioplasted arteries of hypercholesterolemic rabbits: The dose and time effect

PURPOSE To study the dose and time effect of external beam irradiation on the morphometry of both angioplasted and nonangioplasted arteries in a hypercholesterolemic rabbit model. METHODS AND MATERIALS Eight groups of rabbit femoral arteries were studied: arteries (a) with no intervention, (b) irradiated with a 12-Gy 6 MV X-ray dose, (c) with a 18-Gy, (d) treated with balloon angioplasty, (e) dosed with 12-Gy half an hour post-angioplasty, (f) dosed with 18-Gy half an hour post-angioplasty, (g) dosed with 12-Gy 48 h post angioplasty, (g) dosed with 18-Gy 48 h post angioplasty. RESULTS External irradiation at either 12 or 18 Gy was not found to change vessel morphometry in noninjured arteries. The 12-Gy dose given soon after angioplasty further increased percentage stenosis (63% on the average), despite the preservation of the lumen cross-sectional area. Positive remodeling was not observed in arteries given 18-Gy half an hour post angioplasty to counterbalance the increased neointimal formation. Therefore, this treatment resulted in a drastic reduction in lumen area and in enhancement of percentage stenosis (84% on the average). On the contrary, the delayed irradiation of the angioplasted arteries at either 12 or 18 Gy was not found to influence any of the studied morphometric parameters 5 weeks after angioplasty. CONCLUSIONS Uniform external beam irradiation up to 18 Gy was well tolerated by intact femoral arteries. Prompt 12- or 18-Gy irradiations accentuated percentage stenosis. However the lumen cross-sectional area was preserved only at the lower dose point. Delayed irradiation at any dose did not influence the restenosis process.

Elemental composition of bone minerals in women with breast cancer treated with adjuvant tamoxifen

Oestrogen levels play a major role in conditioning the rates of bone changes in women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant therapy for breast cancer. The goal of the present study was to study the amount and the elemental composition of bone minerals in the appedicular skeleton of women with breast cancer treated with adjuvant tamoxifen, as well as to investigate the possibility of increased risk for osteoporosis. Forty-two patients, aged 41–65 years, without skeletal metastases were studied. The mean duration of tamoxifen administration on a daily dose of 20 mg was 21 months (range 1–59 months). It was found that neither the amount of phosphorus in hands (HBP) nor forearm bone mineral content (BMC) differ statistically from those of age-matched healthy subjects. This was confirmed by reassessing bone mineral status after 30 months in 17 postmenopausal patients treated with tamoxifen for a mean time of 52 months. In conclusion, our data support that long-term tamoxifen treatment has no adverse or protective effect on the amount and elemental composition of the appedicular skeleton.