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The possibility of achieving a therapeutically useful tissue boron distribution for boron neutron capture therapy (BNCT) of cerebral gliomas with boron loaded tumor-specific antibodies is discussed. Using a theoretical tumor-immunological model and RBE dose-depth calculations, the effects of various parameters, e.g. antibody-antigen association constant, antigen site density, number of boron atoms per antibody molecule, etc., on the advantage depth, a relative measure of the resulting radiation dose distributions, are determined. It is shown that with this model a maximum in the advantage depth as a function of the blood boron concentration occurs, the position of which is dependent on the value of the parameters used. Frequently this maximum corresponds to a blood boron-10 concentration range of between 0.1 to 0.5 microgram 10B/g blood. It is concluded that given the pharmacodynamic properties of potentially useful antibody preparations for this type of tumor therapy, advantage depths significantly greater than those obtainable with existing "blood-brain-barrier" compounds are not likely to be easily achieved.

The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.

The effects on erythrocyte fragility of two general anaesthetic agents (halothane and ethanol) and succinylcholine were examined using preparations from 13 normal and four malignant hyperthermia susceptible patients. Erythrocyte fragility was determined by the degree of haemolysis induced in solutions of decreasing osmolarity of NaCl. Halothane caused haemolysis of erythrocytes in an isoosmolar solution, being more potent at 42 degrees C than at 32 degrees C. Haemolysis produced by an hypoosmolar medium or halothane was potentiated by exogenously added phospholipase A2. Ethanol did not markedly alter the haemolysis of erythrocytes under conditions of decreasing osmolarity. Succinylcholine 10 mM did not significantly alter the susceptibility of erythrocytes to lysis by halothane. No differences in erythrocyte fragility were observed between preparations from normal and malignant hyperthermia susceptible patients under any of the conditions tested, despite the inclusion of malignant hyperthermia triggering agents in some instances. Although sampling a larger patient population might reveal slight differences between the groups, erythrocyte fragility tests do not appear to be useful in differentiating malignant hyperthermia susceptible from normal patients.

The use of the blood-brain barrier and of tumor-specific antibodies to concentrate boron selectivity in gliomas for neutron capture therapy is considered experimentally and theoretically. The time-dependent concentration of two anionic boranes, B12 H11 SH2- and B12 H11 SOSB12 H114-, in the blood, brain, and tumor of rats bearing a tumor of gliomatous origin is reported. The rate of clearance of each anionic borane from the blood is correlated with the fraction of non-protein bound anion in the plasma. The use of antibodies to carry therapeutical useful amounts of boron to tumor-specific or tumor-associated antigens on the tumor cell surface will require different numbers of boron atoms bound per antibody depending on several immunological and physical parameters. Calculations using published values of antibody-antigen association constants and of cell surface antigen densities predict that in order to obtain 10mug 10B/g tumor from 10 to over 10,000 boron-10 atoms will have to be bound per tumor antigenic site.