Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.
Boron neutron capture therapy (BNCT) is a unique radiation therapy in which boron compounds are trapped into tumor cells. To determine the biodistribution of boronophenylalanine (BPA) in nude mice carrying oral squamous cell carcinoma (SCC), BPA was administered at a dose of 250 mg/kg body weight intraperitoneally. Two hours later, (10)B concentration in the tumor was 15.96 ppm and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 6.44, 4.19, 4.68 and 4.56, respectively. Two hours after the administration of borocaptate sodium (BSH) at a dose of 75 mg/kg body weight, (10)B concentration in the tumor was 3.61 ppm, and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 0.77, 1.05, 0.60 and 0.59, respectively. When cultured oral SCC cells were incubated with BPA or BSH for 2 h and then exposed to thermal neutrons, the proportion of survival cells that were capable of forming cell colonies decreased exponentially, depending on (10)B concentration. BPA-mediated BNCT was more efficient than BSH-mediated BNCT. Addition of boron compounds in the cell suspension during neutron irradiation enhanced the cell-killing effect of the neutrons. These results indicate that BPA is more selectively incorporated into human oral SCC as compared with normal oral tissues, and that both extra- and intra-cellular BPA contribute to the cell-killing effect of BNCT. BPA may be a useful boron carrier for BNCT in the treatment of advanced oral SCC.
Second Department of Oral and Maxillofacial Surgery Osaka University, Graduate School of Dentistry, Osaka 565-0871, Japan.
Shigeki
S
Obayashi
Itsuro
I
Kato
Koji
K
Ono
Shin-Ichiro
S
Masunaga
Minoru
M
Suzuki
Kenji
K
Nagata
Yoshinori
Y
Sakurai
Yoshiaki
Y
Yura
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001895:Boron / Q000032:analysis / Q000097:blood; D001896:Boron Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000503:physiopathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005260:Female; D007554:Isotopes / Q000032:analysis / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000737:chemistry / Q000503:physiopathology / Q000532:radiotherapy*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012062:Relative Biological Effectiveness; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001894:Borohydrides; D001896:Boron Compounds; D007554:Isotopes; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; D001895:Boron; C033685:4-boronophenylalanine