Examination of Stability of p-, m-, o-Boronophenylalanine in Blood with High Performance Liquid Chromatography

Abstract

Many pharmacokinetic experiments were carried out with tumor-bearing animals and patients using p-Boronophenylalanine(p-BPA)-fructose complex, and the selective boron accumulation property in the tumors was confirmed.^1,2 As the results, p-BPA fructose complex has been used for Boron Neutron Capture Therapy (BNCT) of malignant melanoma and brain tumors.^3,4 But, mechanism studies about the accumulation properties are few.⁵ Recently, we have proposed a chemical model representing boron accumulation in and its release from melanoma.⁶ This mechanism is based on the facts that p-BPA is complexed by Dopa, which is greatly produced in melanoma cells, that the complex is then decomposed by tyrosinase to form boric acid. Although the above-mentioned chemical reactions had been rally observed in test tubes, it was still ambiguous whether these reactions do occur or not in a human body. The present paper deals with this point. One of the methods of confirming the phenomena in vivo is ¹¹B-NMR. Since the signal width of boric acid is sharp compared with that of p-BPA and the chemical shift of boric acid is different from that of p-BPA, we can examine whether the decomposition occurs. But, the application of ¹¹B-NMR to the human tissue is not so easy. Improvement of the sample tube and of the NMR module are required.