Analytical techniques for boron and boron 10 analysis in a solid experimental tumor EO. 771.

Abstract

If a tumor can be preferentially loaded with a suitable boron-10 compound and irradiated with thermal neutrons, malignant cells can be selectively destroyed via the alpha-particle + Li 7-nucleus from the reaction 10B(n, alpha)7Li. Neutron capture therapy with two boron-10 amino acid analogs of low toxicity has been tested in recent years: (a) trimethylamine-carboxyborane, (A3) and (b) amine-carboxyborane, (A7). Now the boron-10 glycineamide analog (A8), amineboryl-carboxamide has been synthesized; it contains 13.81% boron (90% Boron 10 + 10% Boron 11) and shows a very low toxicity in mice. The effects of this compound were tested on the syngeneic solid adenocarcinoma EO 771 on the right hind leg of male C57 BL/6J mice under standard conditions, by measuring tumor volume growth delay and cell cycle changes using flow cytometry. Boron distribution between tumor and muscle was analyzed by emission spectroscopy with inductively coupled plasma (ICP) following injection of a suspension of peanut oil emulsion. In addition, boron-10 concentration in the tumor were analyzed with prompt gamma-activation analysis and neutron capture radiography (Kodak-Pathé LR 115) at the MRR reactor in Brookhaven after i.p. injection of 0.4 mg/g A8. Application of A8 alone (0.4 mg/g i.p.) or thermal neutron irradiation of the tumor EO. 771 produced a tumor growth delay of 1-2 days for tumor volume doubling. Application of the boron 10 glycine-amide analog A8 i.p. plus 5 X 10(12)n/cm2 resulted in a growth delay of 3-6 days. In contrast intratumoral application of A8 plus 4 X 10(12)n/cm2 neutrons gave a growth delay of 7-14 days; the fraction of (G2 + M) cells rose from 35% (neutrons alone) to 52%, as evaluated from flow cytometry.