Search

Simple Summary: Neutron capture therapy, or NCT, is a unique irradiation-based method that is used to treat invasive advanced tumors as it minimizes the impact on healthy cells and tissues. Modern neutron sources for NCT include accelerators that can be installed in treatment facilities. One of the main conditions for the successful application of NCT is sufficient accumulation of the drug in tumor cells which allows it to capture neutrons, be activated, and release energy that destroys cancer cells. Among the elements capable of capturing neutrons, boron, gadolinium, and lithium are considered to be the most suitable for NCT. In our study, we showed the results of neutron capture therapy with gadolinium in a group of dogs and cats with spontaneous tumors to clarify the technical aspects of the method while adjusting the treatment conditions as close as possible to those of clinical trials. We conducted a clinical veterinary study on neutron capture therapy (NCT) at a neutron-producing accelerator with seven incurable pets with spontaneous tumors and gadolinium as a neutron capture agent (gadolinium neutron capture therapy, or GdNCT). Gadolinium-containing dimeglumine gadopentetate, or Gd-DTPA (Magnevist®, 0.6 mL/kg b.w.), was used. We observed mild and reversible toxicity related to the treatment. However, no significant tumor regression in response to the treatment was observed. In most cases, there was continued tumor growth. Overall clinical improvement after treatment was only temporary. The use of Gd-DTPA for NCT had no significant effects on the life expectancy and quality of life of animals with spontaneous tumors. Further experiments using more advanced gadolinium compounds are needed to improve the effect of GdNCT so that it can become an alternative to boron neutron capture therapy. Such studies are also necessary for further NCT implementation in clinical practice as well as in veterinary medicine. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as 10B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient 10B concentration within tumors. To address the issue of 10B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that 10B-MMT1242 is a candidate for further clinical BNCT studies. [ABSTRACT FROM AUTHOR]

Abstract: Treatment of malignant spinal cord tumors is currently ineffective. The characteristics of the spine are its seriality, small volume, and vulnerability: severe QOL impairment can be brought about by small neuronal damage. The present study aimed to investigate the feasibility of BNCT as a tumor-selective charged particle therapy for spinal cord tumors from the viewpoint of protecting the normal spine. A previous report suggested the tolerance dose of the spinal cord was 13.8Gy-Eq for radiation myelopathy; a dose as high as 11Gy-Eq demonstrated no spinal cord damage in an experimental animal model. We calculated the tumor dose and the normal spinal cord dose on a virtual model of a spinal cord tumor patient with a JAEA computational dosimetry system (JCDS) treatment planning system. The present study made use of boronophenylalanine (BPA). In these calculations, conditions were set as follows: tumor/normal (T/N) ratio of 3.5, blood boron concentration of 12ppm, tumor boron concentration of 42ppm, and relative biological effectiveness (RBE) values for tumor and normal spinal cord of 3.8 and 1.35, respectively. We examined how to optimize neutron irradiation by changing the beam direction and number. In our theoretical example, simple opposed two-field irradiation achieved 28.0Gy-Eq as a minimum tumor dose and 7.3Gy-Eq as a maximum normal spinal dose. The BNCT for the spinal cord tumor was therefore feasible when a sufficient T/N ratio could be achieved. The use of F-BPA PET imaging for spinal tumor patients is supported by this study. [Copyright &y& Elsevier]