Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.

Abstract

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.

• Authors: Shigeki Obayashi, Itsuro Kato, Koji Ono, Shin-Ichiro Masunaga, Minoru Suzuki, Kenji Nagata, Yoshinori Sakurai, Yoshiaki Yura
• Journal: Oral oncology (Oral Oncol) Vol. 40 Issue 5 Pg. 474-82 (May 2004) ISSN: 1368-8375 [Print] England
• PMID: 15006618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Borohydrides
• Boron Compounds
• Isotopes
• Sulfhydryl Compounds
• mercaptoundecahydrododecaborate
• Phenylalanine
• Boron
• 4-boronophenylalanine

Topics

• Animals
• Borohydrides (administration & dosage, pharmacokinetics)
• Boron (analysis, blood)
• Boron Compounds (pharmacokinetics, therapeutic use)
• Boron Neutron Capture Therapy (methods)
• Carcinoma, Squamous Cell (chemistry, physiopathology, radiotherapy)
• Cell Line, Tumor
• Cell Survival (physiology)
• Female
• Isotopes (analysis, blood)
• Mice
• Mice, Nude
• Mouth Neoplasms (chemistry, physiopathology, radiotherapy)
• Phenylalanine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Relative Biological Effectiveness
• Sulfhydryl Compounds (administration & dosage, pharmacokinetics)