Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound.
As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.
Mishima
Y
Y
Department of Dermatology, Special Institute of Cancer Neutron Capture Therapy, Kobe University School of Medicine, Japan.
Ichihashi
M
M
Tsuji
M
M
Hatta
S
S
Ueda
M
M
Honda
C
C
Suzuki
T
T
D000818:Animals; D001896:Boron Compounds; D005214:Fast Neutrons; D008545:Melanoma / Q000628:therapy*; D009502:Neutrons; D011882:Radiotherapy, High-Energy / Q000379:methods*; D012878:Skin Neoplasms / Q000628:therapy*; D013552:Swine
D001896:Boron Compounds