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This book is the product of a congressionally mandated study to examine the feasibility of eliminating the use of highly enriched uranium (HEU2) in reactor fuel, reactor targets, and medical isotope production facilities.

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope, boron-10, is irradiated with neutrons to produce high energy alpha particles. This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system. Two low molecular weight boron-containing drugs currently are being used clinically, boronophenylalanine (BPA) and sodium borocaptate (BSH). Although they are far from being ideal, their therapeutic efficacy has been demonstrated in patients with high grade gliomas, recurrent tumors of the head and neck region, and a much smaller number with cutaneous and extra-cutaneous melanomas. Because of their limitations, great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use. These include boron-containing porphyrins, amino acids, polyamines, nucleosides, peptides, monoclonal antibodies, liposomes, nanoparticles of various types, boron cluster compounds and co-polymers. Currently, however, none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies. Therefore, at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination, with the hope that future research will identify new and better boron delivery agents for clinical use.

At the end of the Second World War, a diagnosis of cancer was a death sentence. Sixty years later, it is considered a chronic disease rather than one that is invariably fatal. Although survival rates have improved, the very word continues to evoke a special terror and guilt, inspiring scientists and politicians to wage war against it.InUnder the Radar, Ellen Leopold shows how nearly every aspect of our understanding and discussion of cancer bears the imprint of its Cold War entanglement. The current biases toward individual rather than corporate responsibility for rising incidence rates, research that promotes treatment rather than prevention, and therapies that can be patented and marketed all reflect a largely hidden history shaped by the Cold War. Even the language we use to describe the disease, such as the guiding metaphor for treatment, \"fight fire with fire,\" can be traced back to the middle of the twentieth century.Writing in a lucid style, Leopold documents the military, governmental, industrial, and medical views of radiation and atomic energy to examine the postwar response to cancer through the prism of the Cold War. She explores the role of radiation in cancer therapies today, using case studies and mammogram screening, in particular, to highlight the surprising parallels. Taking into account a wide array of disciplines, this book challenges our understanding of cancer and how we approach its treatment.Examines the postwar response to cancer through the prism of the Cold WarGoes beyond medical science to look at the influence of Cold War policies on the way we think about cancer todayLinks the experience of postwar cancer patients with the broader evolution of what have become cancer industriesTraces the history of human-made radiation as a state-sponsored environmental toxin

The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves, the doses required for a GI of 0.37 (D37) were derived, and the RBE of 211At was calculated. The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.

「Carbon beam therapy/Uterine cervix/p53/Ki-67/p27. 」Little clinical evidence has been provided to show the minimization of radiation resistance of tumors using high linear energy transfer radiation. We therefore investigated the radiobiological and molecular pathological aspects of carbon beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the cervix were treated using a carbon beam and 50 control patients with SCC of the cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before radiotherapy and 5 and 15 days after therapy initiation were investigated using immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI) and p53 LI during carbon and photon beam therapies. However, for carbon beam therapy, the mean p27 LI significantly decreased from 25.2% before treatment to 18.6% on the 5th day after treatment initiation, followed by a significant increase to 36.1% on the 15th day. In contrast, for photon beam therapy, the p27 LI consistently decreased from the initial 19.9% to 13.7% on the 15th day. Histological effects were observably stronger under carbon than photon beam therapy, though no statistically significant difference was observed (p=0.07 on the 5th day and p=0.10 on the 15th day). The changes in p27 LI under carbon beam therapy were significantly different from those under photon beam therapy, which suggests important molecular differences in the radio-biological response between therapies. Further investigation is required to elucidate the clinical relevance of these putative changes and optimize the relative biological effectiveness of carbon beam to X-ray.

This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable H/ H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with O/ O/ O, N/ N, C/ C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The comparative analysis of some experimental studies results revealed the following observation: \"Isotopic shock\" is highly probable and is observed mostly when chemical bonds form between atoms with a summary odd number of neutrons (i.e., bonds with a non-compensated neutron, which correspond to the following equation: Nn - Np = 2k + 1, where k ϵ Z, k is the integer, Z is the set of non-negative integers, Nn is number of neutrons, and Np is number of protons of each individual atom, or in pair of isotopes with a chemical bond). Data on the efficacy and metabolic pathways of the therapy also considered H-modified drinking and diet for some diseases, such as Alzheimer's disease, Friedreich's ataxia, mitochondrial disorders, diabetes, cerebral hypoxia, Parkinson's disease, and brain cancer.

We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method-(23)Na-MRI-in comparison to a standard contrast-enhanced (1)H-MRI and (18)F-FET-PET. A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up (1)H-MRI and a (18)F-FET-PET were performed. In addition, an IRB-approved (23)Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, (23)Na content, and increased uptake in the (18)F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the (23)Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the (18)F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower (23)Na content compared to areas with suspected proliferating tumor tissue. (23)Na-MRI provided similar information in the suspicious area compared to (18)F-FET-PET, exceeding conventional (1)H-MRI. Still, (23)Na-MRI remains an investigational technique, which is worth to be further evaluated.

This paper summarizes outcomes of a single-center study of intracavitary brachytherapy (IBT) with stereotactically applied phosphorus-32 ( 32 P) colloid for treatment of cystic craniopharyngiomas. We assessed its efficacy and safety, on the basis of clinical and radiological outcomes in one of the largest reported patient series. Between 1992 and 2011, 53 patients were treated with IBT, 14 without previous treatment and 39 who had previously been treated for recurrent cysts. Intervention was performed by applying 200 Gy to the internal cyst wall (median volume 6.1 ml). Median clinical and radiological follow-up were 60.2 and 53.0 months, respectively. Actuarial tumor cyst control was 86.0 ± 5.3 % at 12, 24, and 60 months. Actuarial out-of-field control (development of new cysts or progression of solid tumor parts) was 90.9 ± 4.3, 84.0 ± 5.6, and 54.5 ± 8.8 % after 12, 24, and 60 months, respectively. Corresponding actuarial overall progression-free survival was 79.4 ± 6.1, 72.4 ± 6.8, and 45.6 ± 8.7 % at 12, 24, and 60 months, respectively. Visual function improved for 12 patients (23.5 %), remained unchanged for 34 patients (66.7 %), and worsened for five patients (9.8 %), correlating with tumor progression in each case. Endocrinological deterioration occurred for ten patients (19.6 %); for nine patients this was a result of tumor progression or after tumor resection and for one it was attributed to irradiation. Within six months of IBT seven patients (13.7 %) experienced transient neurological deficits and two patients (3.9 %) deteriorated permanently (hemiparesis and third nerve palsy). Stereotactically applied 32 P is highly efficacious for control of cystic components of craniopharyngiomas and is associated with a low risk of permanent morbidity. The procedure does not, however affect the development of new cysts or the progression of solid tumor parts.

The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the photoelectric effect, pair production, Rayleigh scattering and bound Compton scattering were included in the simulation. Variance reduction techniques were used to speed up the calculation and to considerably reduce the computer time. The cut-off energy was 10 keV for electrons and photons. To obtain the dose rate distributions of the source in an unbounded liquid water phantom, the source was immersed at the center of a cube phantom of 100 cm3. The liquid water density was 0.998 g/cm3, and photon histories of up to 1010 were used to obtain the results with a standard deviation of less than 0.5% (k = 1). The obtained dose rate constant for the BEBIG 60Co source was 1.108±0.001 cGyh-1U-1, which is consistent with the values in the literature. The radial dose functions were compared with the values of the consensus data set in the literature, and they are consistent with the published data for this energy range.

Less invasive aspiration of cystic contents only provides a temporary solution, with cysts tending to refill and expand after a single drainage.1 The beneficial effects of intracavitary irradiation for treatment of cystic craniopharyngiomas as a means to abolish the secretory capability of the cyst’s epithelial lining, while sparing nearby critical brain structures, has been previously reported.2-4 90Yttrium colloid is considered a suitable isotope for treatment of cystic craniopharyngiomas because of its short half-life and pure β emission.1,2 Intracavitary irradiation with stereotactically implanted 90yttrium colloid has been shown to be effective in long-term shrinkage of the cystic portion of recurrent craniopharyngiomas. METHODS As part of a Health Canada Phase III clinical trial (NCT02081768), informed consent was obtained from patients treated with 90yttrium colloid for a suprasellar cystic craniopharyngioma (surgical methods described elsewhere3) to undergo PET-CT 24 to 48 hours postoperatively. Image fusion to anatomical imaging (CT and/or MRI) confirms successful injection into the target site, assesses the distribution of 90yttrium colloid within all of the cyst, and may provide a means to evaluate leakage of 90yttrium colloid.