Boron Neutron Capture Therapy and Targeted Alpha Therapy for Intractable Cancers Combined with Positron Emission Tomography/Computed Tomography

The boron neutron capture therapy (BNCT) is based on the cell-killing effect of α-particle and lithium-particle produced in the body by 10B (n, α) 7Li nuclear transmutation reaction after 10B delivery to target cancer cells and local irradiation of neutron. Neutron source was initially a nuclear reactor, and recently in-house accelerator. 10B delivery molecule was 10B-boronophenylalanine (10B-BPA), which was transported into cancer cells through L-type amino acid transporter 1 (LAT1) predominantly expressed on the membrane of cancer cells. 18F-fluor- -boronophenylalanine (18F-FBPA) was a PET probe to estimate 10B-BPA accumulation in the target tumor and surrounding normal tissue. The BNCT was recently approved as a treatment of head and neck cancer in Japan. The targeted α therapy (TAT) employed α-particle emitting radioisotopes mainly to metastatic cancers. The element 85, 211At with physical half-life of 7.2 hours, belongs to halogen family in the Periodic Table. Its distribution was similar to 131I. We are now trying to apply 211At to treat intractable thyroid cancers and other types of advanced cancers. Preclinical studies with 211At labeled LAT1 compounds including 211At-phenylalanine (211At-Phe) and 211At-α-methyl tyrosine (211At-AAMT) demonstrated their tumor growth suppression effect on the xenograft model of glioblastoma and pancreatic cancer in rats, respectively. 18F-fluor- -phenylalanine (18F-FPhe) and 18F-fluoro-α-methyl-tyrosine (18F-FAMT) are PET probes to study their accumulation to cancers, respectively. The BNCT and the TAT combined with PET/CT imaging may provide effective treatment of intractable and/or metastatic cancers.