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To optimize the neutron dose for boron neutron capture therapy (BNCT), the boron-10 (10B) concentration kinetics of 10B-p-boronophenylalanine (BPA) were analysed in 22 melanoma patients with primary or metastatic melanomas who received BPA and subsequently underwent BNCT or surgery. The blood concentration in nine patients receiving 179.7+/-14.9 mg/kg BPA increased with time during intravenous infusion, peaked at the end of administration and decreased thereafter. The peak values at the end of administration were 9.4 2.6 microg 10B/g blood, and half-lives for the initial and second components of the blood clearance were 2.8 and 9.2 h, respectively. Skin concentrations in the 10 patients varied from case to case; however, skin-to-blood ratios were relatively constant at 1.31+/-0.22 during the 6 h after the end of administration. Boron concentrations in the tumours resected from the seven patients who were operated on decreased in parallel to the blood values, the tumour-to-blood ratio being relatively constant at 3.40+/-0.83. The present analytical data of BPA pharmacokinetics support our previous approach for optimizing the timing of irradiation and setting the neutron flux large enough for tumour eradication but still tolerable for normal skin.

We have developed neutron-capture therapy (NCT) for cutaneous malignant melanoma using a melanoma-seeking 10B-dopa, analogue, 10B1-para-boronophenylalanine (10B1-BPA). In order to explore the feasibility of applying NCT further to ocular melanoma, we investigated the boron concentrations in ocular melanomas and normal ocular tissues by 10B1-BPA administration to three patients, because success of NCT depends mainly upon selective boron accumulation in melanoma. In the first and second ocular melanoma patients, to whom 10B1-BPA fructose complex (total dose of 10B1-BPA: 170 mg/kg body weight) was administered orally in two divided doses, the boron concentrations in blood, vitreous body, sclera and retina choroidea were lower than that in melanoma examined. In the third conjunctival melanoma patient, to whom 10B1-BPA fructose complex (dose of 10B1-BPA: 85 mg/kg body weight) was administered by intravenous drip infusion, the average boron concentration in four melanoma samples was 17.7 ppm, which was estimated to be within the range necessary for melanoma eradication by thermal neutron irradiation. Boron uptake by lens, vitreous body, retina choroidea and sclera was much lower than that by melanoma. It was suggested that such a superficial ocular melanoma as iris melanoma can be destroyed by NCT, although vision may be affected--mainly due to cataract formation.

Research on selective melanoma neutron capture therapy was initiated by Y. Mishima and his associates, consisting of physicists, chemists, pharmacologists, radiobiologists, and medical scientists. Following basic research of 13 years, this team started the first clinical. trial of melanoma BNCT using10B-paraboronophenylalanine (BPA) in 1987 and have treated 16 patients with various types of melanoma1−4.

Success of boron neutron capture therapy (NCT) for cancer depends mainly upon selective boron accumulation in the targeted tumor. Since 1987 we have succeeded in treating human melanoma lesions by NCT utilizing10B1-para-boronophenylalanine (10B1-BPA).1 At the same time we have investigated various methods of administering10B1-BPA for optimal NCT. The results of our analytical studies on boron kinetics in animals and humans by 10B1-BPA administration are described.

Due to the wide variation in biological systems, criteria, dose, and experimental conditions used to determine relative biological effectiveness (RBE) it is necessary to re-evaluate the experimental RBE for human treatment. In this paper, the biological effect of 10B-neutron capture therapy (BNCT) on human skin is re-evaluated based on the skin RBE value of hamsters.

We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976–1980 with those who attended between 1986–1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986–1990 were higher than those from 1976–1980, In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III.

We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976-1980 with those who attended between 1986-1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986-1990 were higher than those from 1976-1980. In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100,000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III. The present study indicates that the prevalences of NMSC and SK in Japanese have increased during the last three decades and that skin type I may be a risk factor for NMSC in Japanese.

The success of treatment of tumors with NCT lies primarily with the development of suitable vectors to optimally carry 10B to the tumor site, efficient methods of their administration, and effective neutron beam delivery.

We have succeeded in curing primary cutaneous malignant melanomas of human patients by neutron capture therapy (NCT) using 10B1-para-boronophenylalanine (10BPA)1,2. Since primary cutaneous melanomas are usually within l0mm in thickness, we can irradiate the whole primary lesions with thermal neutrons in a sufficient dose for eradication. In further applying our NCT to deep-seated melanoma lesions, especially those metastasizing into the lymph nodes, partial replacement of hydrogen (H) with deuterium (D) (deuteriation or deuteration) is expected to improve the penetration of thermal neutrons into the depth of the tumors due to the decreased H(n,g)D reaction and very low cross section of D for neutron capture.

We have previously shown that 10B1-paraboronophenylalanine (10B1-BPA) has selective affinity for both melanotic and amelanotic melanomas in vitro and in vivo1). We have also shown complete suppression of implanted melanoma in hamster by thermal neutron capture therapy (NCT) using 10B1- BPA1). Further, we have already treated succesfully six human melanoma cases by NCT using 10B1-BPA1,2).

10B1-para-Boronophenylalanine(10B1-BPA) has selective affinity for malignant melanoma. In our first human case, we succeeded in obtaining complete regression of a metastatic subcutaneous melanoma lesion by neutron capture therapy (NCT) using distant perilesional injections of 10B1-BPA hydrochloride.