Large animal normal tissue tolerance with boron neutron capture

Area of Science:

• Radiation oncology
• Medical physics
• Boron neutron capture therapy

Background:

• Boron neutron capture therapy (BNCT) is an investigational cancer treatment.
• Borocaptate sodium (BSH) is a boron-containing compound used in BNCT.
• Understanding normal tissue tolerance is crucial for BNCT efficacy.

Purpose of the Study:

• To evaluate the normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam.
• To determine dose-limiting toxicities and observe long-term effects in canine models.

Main Methods:

• Large retriever dogs were used for irradiation studies.
• Irradiations were performed using a single dose, 5 x 10 dorsal portal epithermal neutron beam.
• Dogs received either epithermal neutrons alone (14 dogs) or following intravenous administration of borocaptate sodium (35 dogs).

Main Results:

• Total body irradiation effects included decreased leukocytes and platelets, with most values normalizing within 40 days.
• Severe dermal necrosis occurred at 15 Gy (neutrons alone) and >64 Gy (with BSH).
• Lethal brain necrosis was observed between 27-39 Gy, occurring 22-36 weeks postirradiation. Abnormal MRI findings at 6 months post-27 Gy with 25-50 ppm boron resolved by 12 months in most dogs.

Conclusions:

• BNCT with BSH presents challenges for dose-response assays due to mixed LET components.
• The short track length of boron fission fragments and vascular geometry may reduce the dose to endothelial cells.
• A significant dose-sparing effect from boron capture reactions within the blood was indicated.