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.

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

Microbeam radiation therapy is an experimental modality using parallel arrays of thin (<100 micro m) slices of synchrotron-generated X rays (microplanar beams, microbeams). We used EMT-6 murine mammary carcinoma subcutaneously inoculated in the hind legs of mice to compare the therapeutic efficacies of single-fraction, unidirectional (1) "co-planar" microbeams (an array of vertically oriented microplanar beams), (2) "cross-planar" microbeams (two arrays of parallel microbeams propagated in the same direction, one with vertically and the other with horizontally oriented microplanar beams), and (3) seamless (broad) beams from the same synchrotron source. The microbeams were 90 micro m wide and were spaced 300 micro m on center; the median energy in all beams was 100 or 118 keV. Tumor ablation rates were 4/8, 4/8 and 6/7 for a 410-, 520- and 650-Gy in-slice cross-planar microbeam dose, respectively, and 1/8, 3/8, 3/7 and 6/8 for a 23-, 30-, 38- and 45-Gy broad-beam dose, respectively. When the data were pooled from the three highest doses (same average tumor ablations of 50-60%), the incidences of normal-tissue acute toxicity (moist desquamation and epilation) and delayed toxicity (failure of hair regrowth) were significantly lower for cross-planar microbeams than broad beams (P < 0.025). Furthermore, for the highest doses in these two groups, which also had the same tumor ablation rate (>75%), not only were the above toxicities lower for the cross-planar microbeams than for the broad beams (P < 0.02), but severe leg dysfunction was also lower (P < 0.003). These findings suggest that single-fraction microbeams can ablate tumors at high rates with relatively little normal-tissue toxicity.

No abstract

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

An x-ray fluorescence system which utilizes polarized radiation to measure lead in vivo in human subjects is described. The minimum detection limit is approximately 6.4 ppm wet weight lead in the cortex of the tibia with 4 mm of overlying soft tissue. This appears to be adequate for assessing lead stores in lead-toxic preschool children. The measurement requires 16.5 min and is associated with an effective equivalent whole body dose to the subject of 2.5 muSv. The system, its calibration and its validation are described herein.

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.

Mild to moderate lead toxicity (blood lead, 25-55 ,ag/dl) is a preventable pediatric illness affecting several million preschool children ("lead-toxic children") in the United States. In-hospital lead-chelation treatment is predicated upon a positive CaNa2EDTA test, which is difficult to perform and impractical in large populations. After the development of an L-line x-ray fluorescence technique (LXRF) that measures cortical bone lead content safely, rapidly, and noninvasively, this study was initiated in lead-toxic children to compare LXRF with the CaNa2EDTA test. Moreover, LXRF provided the opportunity to quantify bone lead content. From blood lead and LXRF alone, 90% of lead-toxic children were correctly classified as being CaNa2EDTA-positive or -negative. In 76% of 59 lead-toxic children, bone lead values measured by LXRF were equal to or greater than those measured in normal and industrially exposed adults. These results indicate that LXRF may be capable of replacing the CaNa2EDTA test. When considered with the known neurotoxic effects on children of "low levels" of exposure to lead, these results also suggest that either an excessively narrow margin of safety or insufficient safety is provided by present U.S. guidelines, which classify an elevated blood lead concentration as 25 jug/dl or greater.Environmental Pb exposure is a continuing health hazard for American children (1). Pb toxicity, defined as a blood Pb