In Vivo Accelerator-Based Boron Neutron Capture Therapy for Spontaneous Tumors in Large Animals: Case Series

Abstract

(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

Gadolinium Neutron Capture Therapy for Cats and Dogs with Spontaneous Tumors Using Gd-DTPA

“…Animal positioning during therapy, collection of blood samples for analysis, and post-treatment monitoring of the animals for three months were performed according to the methodology of the previous study [50].…”

“…NCT is designed to be applied mainly in head and neck cancer, intracerebral tumors, melanoma, and metastatic lesions, which are very common in pets. We are the first to conduct a preclinical GdNCT effectiveness study in large mammals with malignant tumors using a registered gadolinium-containing MRI contrast agent, Magnevist ® (dimeglumine gadopentetate), and a neutron beam obtained at the accelerator developed at the Institute of Nuclear Physics in Novosibirsk, Russian Federation [49] with irradiation conditions similar to those in our previous experiments on BNCT [50].…”

Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer

“…After intravenous injection of BPA (125 mg/kg body weight) to six 8-week-old male SD rats, the blood was collected from the eye at 5,10,15,20,25,30,40,50,60,90,120,150, and 180 min under anesthesia using isoflurane. One hundred microliters of blood was used for the determination of boron concentration using the ICP-AES assay.…”

“…High selectivity of boron in tumor tissue rather than that in blood or normal tissues prior to neutron irradiation is required for the successful treatment of tumors using BNCT ( 15 ). In addition, evaluation of boron levels in a tumor is required for dosimetric modeling in BNCT ( 5 , 16 ). Whole blood concentrations of boron can be used as a surrogate for measuring the boron content in the in vivo tissue.…”

“…Boron neutron capture therapy (BNCT) is a radiation therapy at the cellular level and combines neutron irradiation with the boron compounds selectively delivered to tumor tissue (1)(2)(3), depending on the nuclear capture and fission reactions (4). These reactions occur when 10 B, a non-radioactive boron isotope, is irradiated with thermal neutrons to yield a-particles and lithium-7 nuclei with an almost one-cell diameter (5). Therefore, BNCT links two fundamental approaches, i.e., chemotherapy and traditional radiotherapy.…”