Susumu Hatta

Selective Thermal Neutron Capture Therapy and Diagnosis of Malignant Melanoma: From Basic Studies to First Clinical Treatment

As melanoma genesis occurs in pigment cells, accentuated melanogenesis concurrently occurs in principlel. Thus, harnessing this accentuation of melanogenesis, we developed a new mutually-dependent two-step therapy, in which melanogenesis-seeking compounds first specifically target melanoma cells, enabling the powerful second step to selectively destroy the targeted cells. Our new thermal neutron capture therapy2,3,4,5(NCT) uses a 10B-dopa(melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA) which accumulates preferentially in melanoma cells6,7. The cells then are irradiated with thermal neutrons to induce the 10B(n, α)7Li reaction which releases energy of 2.33MeV to a distance of 10~14μ, the diameter of melanoma cells. Extensive in vitro and in vivo radiobiological analysis8 confirmed the highly enhanced killing effect of 10B1-BPA. Measurements of the accumulating capacity of 10B1-BPA into melanoma cells in vitro and in vivo using both chemical and prompt gamma ray spectrometry7 assay showed its high affinity for these cells9.

Effects of L‐glutamine on Tyrosinase and γ‐glutamyl Transpeptidase of B‐16 Melanoma Cells in Culture

Omission of L‐glutamine (Gln) from the culture medium decreases tyrosinase activity and increases γ‐GTP activity in cultured melanotic B‐16 melanoma cells; inclusion of this amino acid in the medium shows the reverse effects. Its absence, however, decreases the γ‐GTP activity in non‐pigmented cells like HeLa cells, fibroblasts and amelanotic melanoma cells and its presence induces a dose dependent increase in this enzyme activity in these cells. The decrease of γ‐GTP activity in the melanotic melanoma cells by Gln is attributed to increased production of dopa and its derivatives by these cells, as evidenced by our results. Our data also indicate the inhibitory effects of dopa and several other dopa derivatives known to be produced by the melanoma cells on isolated bovine kidney γ‐GTP.