Tissue Distribution of Boron Compounds in Relation to Neutron-Capture Therapy of Cancer.

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Abstract
Recent application of the atomic pile to neutron-capture therapy of human brain tumors has focused attention on the biologic behavior of boron compounds. Boron-10 on capture of a thermal neutron instantly disintegrates with release of therapeutically useful high energy heavy particles with a range in tissue of 10-15[mu]. Studies in this laboratory demonstrated that a favorable concn. ratio of better than 3 to 1 exists between malignant tumors and normal brain, and that borax and boric acid are rapidly absorbed and distributed throughout the body in mice and man. In mice the uptake by various organs and tumor describes a family of similar curves such that the faster the rise in concn., the higher and earlier is peak concn.. All tissues studied, except brain, reach a peak by 30 min.. Borate is rapidly excreted by the kidneys as a "low-threshold substance" in a class with urea and sulfate, and clearance from the blood in mice proceeds with an approx. exponential half-time of 65 min.. Concns. of borate in the tissues of normal mice are directly proportional to dosage for at least 2 hrs. after injn. over a range of 18 to 700 gamma/g. body wt. At equilibrium distr., studied in nephrectomized mice, borate is uniformly distr. throughout the body water, with a 10 to 20% excess bound in the intracellular compartment. This excess is bound more tenaciously in brain than in other tissues and appears to be responsible for the toxicity of these compounds. Study of the factors determining the concn. ratio between neoplasm and surrounding normal tissues indicates that boron-neutron treatment offers little promise for malignant tumors other than those of the brain.

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