Cerebrospinal fluid-based boron delivery system may help increase the uptake boron for boron neutron capture therapy in veterinary medicine: A preliminary study with normal rat brain cells.

Boron neutron capture therapy (BNCT) is a non-invasive type of radiation therapy developed for humans and translated to veterinary medicine. However, clinical trials on BNCT for patients with brain tumors are on-going. To improve the therapeutic efficacy of BNCT for brain tumors, we developed a boron delivery system that involves the cerebrospinal fluid (CSF), in contrast to the conventional method that involves intravenous (IV) administration. This study aimed to investigate the time-concentration profile of boron in the CSF as well as the uptake rate of boron by the brain cells after administering L-p­boronophenylalanine (BPA) into the lateral ventricle of normal rats. Brain cell uptake rates were compared between the CSF-based and IV administration methods. The CSF-based and IV administration methods achieved comparable brain cell uptake levels; however, the former method involved lower BPA doses than the latter method. These findings suggest that the CSF method may reduce the economic and physical burdens associated with this treatment in brain tumor patients. Future studies should validate these findings in rat models of brain tumors.

Dose estimation of animal experiments at the THOR BNCT beam by NCTPlan and Xplan.

Dose estimation of animal experiments affects many subsequent derived quantities, such as RBE and CBE values. It is important to ensure the trustiness of calculated dose of the irradiated animals. However, the dose estimation was normally calculated using simplified geometries and tissue compositions, which led to rough results. This paper introduces the use of treatment planning systems NCTplan and Xplan for the dose estimation. A mouse was taken as an example and it was brought to hospital for micro-PET/CT scan. It was found that the critical organ doses of an irradiated mouse calculated by simplified model were unreliable in comparison to Xplan voxel model. The difference could reach the extent of several tenths percent. It is recommended that a treatment planning system should be introduced to future animal experiments to upgrade the data quality.

Comparison of BNCT and GdNCT efficacy in treatment of canine cancer.

In this study efficacy of antineoplastic action of gadolinium NCT and boron NCT in cases of canine melanoma and osteosarcoma was compared. Canine spontaneous tumors, such as melanoma and osteosarcoma, have clinical common features with human malignancies, so these tumors in dogs can be considered as clinical model of human melanoma and osteosarcoma. The study has been carried out on 33 dogs with oral cavity melanoma and 9 dogs with osteosarcoma. Dogs with spontaneous melanoma of oral cavity and osteosarcoma of extremities were selected by the results of clinical examination. Irradiation was carried out at the NCT facility of the IRT MEPhI reactor. Neutron irradiation without boron or gadolinium was chosen as a control method to evaluate the efficacy of NCT.

Biodistribution of p-borophenylalanine (BPA) in dogs with spontaneous undifferentiated thyroid carcinoma (UTC).

Human undifferentiated thyroid carcinoma (UTC) is a very aggressive tumor which lacks an adequate treatment. The UTC human cell line ARO has a selective uptake of BPA in vitro and after transplanting into nude mice. Applications of boron neutron capture therapy (BNCT) to mice showed a 100% control of growth and a 50% histological cure of tumors with an initial volume of 50 mm(3) or less. As a further step towards the potential application in humans we have performed the present studies. Four dogs with diagnosis of spontaneous UTC were studied. A BPA-fructose solution was infused during 60 min and dogs were submitted to thyroidectomy. Samples of blood and from different areas of the tumors (and in one dog from normal thyroid) were obtained and the boron was determined by ICP-OES. Selective BPA uptake by the tumor was found in all animals, the tumor/blood ratios ranged between 2.02 and 3.76, while the tumor/normal thyroid ratio was 6.78. Individual samples had tumor/blood ratios between 8.36 and 0.33. These ratios were related to the two histological patterns observed: homogeneous and heterogeneous tumors. We confirm the selective uptake of BPA by spontaneous UTC in dogs and plan to apply BNCT in the future.

BNCT of 3 cases of spontaneous head and neck cancer in feline patients.

Having demonstrated BPA-BNCT induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of the RA-1 Reactor within a preclinical context. The biodistribution studies showed that, in all three cases evaluated, BPA delivered absolute boron values to tumor in the range that proved therapeutically useful in the experimental model of SCC. BPA-BNCT studies showed no radiotoxic effects, partial tumor control in terms of impaired growth and partial necrosis, an improvement in clinical condition and prolonged survival beyond the terminal condition of the feline patients at the time of recruitment.