The Chemistry of Neutron Capture Therapy.

A therapeutic method that selectively destroys malignant cells in the presence of normal cells is a highly valued goal of oncologists and the possible salvation of cancer patients afflicted with some incurable forms of the disease. Selective cell destruction is, in principle, possible with a binary therapeutic strategy based upon the neutron capture reaction observed with the 10B nucleus and a neutron of low kinetic energy (thermal neutron). This nuclear fission reaction produces both 4He and 7Li+ nuclei along with about 2.4 MeV of kinetic energy and weak γ-radiation. Since the energetic and cytotoxic product ions travel only about one cell diameter in tissue one may specify the cell type to be destroyed by placing innocent 10B nuclei on or within only the doomed cells. This article describes the current status of chemical research aimed at the eventual adoption of this therapeutic method (boron neutron capture therapy or BNCT). The multidisciplinary nature of this research effort involves chemistry, biology, nuclear physics, medicine, and related specialties. Methods devised for bringing 10B nuclei to tumor cells in therapeutic amounts are correlated with the structure of a generalized cell and the various cellular compartments available for boron localization. The synthesis methods employed for the creation of boron-containing biomolecules and drugs are presented along with representative data concerning their efficacy in tumor localization. The outlook for BNCT is especially bright at this time because of rapid developments in the fields of bioorganometallic chemistry, microbiology, immunology, and nuclear science, to name but a few. Very effective boron delivery vehicles have been demonstrated, and through the interaction of chemistry and biology these species are undergoing further improvement and evaluation of their suitability for BNCT.

The Role of Chemistry in the Development of Boron Neutron Capture Therapy of Cancer

The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (SMR) and cumulative mortality rate were significantly high in blackfoot disease-endemic areas for cancers of bladder, kidney, skin, lung, liver, and colon. The SMRs for cancers of bladder, kidney, skin, lung, liver, and colon were 1100, 772, 534, 320, 170, and 160, respectively, for males, and 2009, 1119, 652, 413, 229, and 168, respectively, for females. A dose-response relationship was observed between SMRs of the cancers and blackfoot disease prevalence rate of the villages and townships in the endemic areas. SMRs of cancers were greater in villages where only artesian wells were used as the drinking water source than in villages using both artesian and shallow wells, and even greater than in villages using shallow wells only.

https://cancerres.aacrjournals.org/content/canres/45/11_Part_2/5895.full.pdf

Malignant Neoplasms among Residents of a Blackfoot Disease-endemic Area in Taiwan: High-Arsenic Artesian Well Water and Cancers

The medicinal chemistry of carboranes

Applications of Radiolabeled Boron Clusters to the Diagnosis and Treatment of Cancer

Introduction During the evolution of brain-tumor localization by means of positron-emitting radioactive isotopes over the past four years, a large amount of data on the behavior of inorganic arsenic in man has been accumulated.1,2The experimentally determined distribution and turnover of radioarsenic (As74) in normal tissues, as well as in various intracranial neoplasms from over 100 patients studied, constitute the material of this report. Methods A. Preparation and Administration of the Isotope. As74is produced by deuteron bombardment of germanium powder in the cyclotron. A modification of the separation described by Green and Kafalas3is now used to obtain carrier-free activity, largely as the trivalent arsenite. In this procedure, the irradiated germanium powder is dissolved in nitrohydrochloric acid (aqua regia) and the germanium driven off as the tetrachloride gas by heating. Hydrobromic acid is added to reduce the arsenic to the trivalent state, and the latter

Radioarsenic in plasma, urine, normal tissues, and intracranial neoplasms; distribution and turnover after intravenous injection in man.

Moore1first reported in 1948 his pioneer efforts to localize brain tumors by external counting of the gamma radiation from diiodofluorescein labeled with iodine 131. The method consists of intravenous injection of the radioactive substance and subsequent measurement of gamma radiation emerging from the head by means of a suitable detector placed at various positions on the scalp. The presence of a tumor is indicated by a reading of asymmetrical activity or by divergence from a pattern of normal observations. At the same time, Selverstone and Solomon2were demonstrating that the beta emitter phosphorus 32 injected as the phosphate would also localize in brain tumors. The localization and demonstration of these lesions by a probe counter during operation has since become an accurate, routine procedure with us.3The precision of the method has been shown in postmortem material by Selverstone and White.4A useful technique for

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=300056&pdfFileName=jama_157_14_002.pdf

Localization of intracranial lesions by scanning with positron-emitting arsenic.

The nuclei of the principal atoms found in normal living tissue have but little tendency to capture very slow (thermal) neutrons, whereas the nuclei of a certain few isotopes have a remarkable propensity for capture of thermal neutrons. Among the isotopes in the latter group, boron'0 (B10) attracted the attention of Kruger (1) and of Zahl, Cooper, and Dunning (2) as early as 1940 because the capture reaction yields a high energy alpha particle which dissipates all its energy in tissue within circa 14 a. The reaction may be written:

/pdf/the-possible-use-of-neutron-capturing-isotopes-such-as-4suwufr3a3.pdf

The possible use of neutron-capturing isotopes such as boron10 in the treatment of neoplasms. ii. computation of the radiation energies and estimates of effects in normal and neoplastic brain

Copper versenate injected intravenously in man achieves within 2 hours concentrations in metastatic tumors about 9 times and in more rapidly growing gliomas about 5 times those in normal brain. Concentrations of copper in muscle rise steadily whereas those in tumor and normal brain fall. Copper scanning, best carried out within an hour of injection, has detected about 55 per cent of a random series of intracranial tumors. In the same patients arsenic scans detected 76% of the tumors. However, some tumors were detected by copper in which the arsenic failed. Vascular lesions of the brain are less likely to yield a positive scan with copper than with arsenic. About 5% of an intravenously injected dose of copper versonate is excreted in the urine. The rest largely undergoes physical decay of its activity before excretion occurs. The Cu64 activity injected for a diagnostic scan gives a whole-body radiation dosage of 0.33 rad, which is about the weekly permissible dose for personnel constantly exposed to radiation. Hence, this diagnostic maneuver may be repeated several times with impunity.

Positron-scanning with copper-64 in the diagnosis of intracranial lesions: partition of copper-64 versenate in, and excretion from, the body.

Many of the reports of studies on experimental cerebral emboli have described the clinical effects or the pathological picture with the purpose of a better understanding of cerebrovascular diseases. A smaller number have stressed the influence of size and number of the injected particles (16). It has seemed to us that a contribution to the problem might be made by the use of radioactive material which would permit acquisition of quantitative data on the distribution of particles within specific ranges of size. A further use of radioactive artificial emboli is that of Muller and Rossier (12) who have used the filtering action of the pulmonary capillaries as a means of concentrating in the lungs a source of internal radiation in an effort to treat pulmonary cancer. Ginell (7) has suggested that this principle may have general applicability. The brain seemed to us a reasonably favorable organ for preliminary trials, due to the relative ease of puncturing any one of its 4 main nutrient arteries, the possibility of precise localization of a tumor in one or more of the arterial fields of supply, and the absence of metastases in gliomas. Moreover, a high sensitivity to radiation in the case of multiple brain metastases is a favorable likelihood. Finally, the particles which cross or by-pass the brain should be arrested by the lung capillaries, with a minimal hazard for the liver or hematopoietic organs.

Gordon L. Brownell

Papers

Radioarsenic in plasma, urine, normal tissues, and intracranial neoplasms; distribution and turnover after intravenous injection in man.

Localization of intracranial lesions by scanning with positron-emitting arsenic.

The possible use of neutron-capturing isotopes such as boron10 in the treatment of neoplasms. ii. computation of the radiation energies and estimates of effects in normal and neoplastic brain

Positron-scanning with copper-64 in the diagnosis of intracranial lesions: partition of copper-64 versenate in, and excretion from, the body.

The fate of radioactive emboli injected into the cerebral circulation, the brain as a filter.