The Evolution of Radionanotargeting towards Clinical Precision Oncology: A Festschrift in Honor of Kalevi Kairemo

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

Author(s): Jun Hatazawa *

Pp: 295-308 (14)

DOI: 10.2174/9781681088655122010028

* (Excluding Mailing and Handling)

Abstract

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.


Keywords: BNCT, High Linear Energy Transfer, Pancreatic Cancer, PET tracer, Targeted α Therapy.

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