Application of BNCT to the treatment of HER2+ breast cancer recurrences: Research and developments in Argentina.

In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research.

Terapia da Captura de Nêutrons pelo Boro (BNCT) no tratamento do Câncer

A terapia de captura de nêutrons pelo boro (BNCT – Boron Neutron CaptureTherapy) é uma ferramenta terapêutica para o tratamento de diversos tipos detumores. É baseada na administração de um composto que contenha o isótopo 10do elemento boro (10B), seguido de irradiação com nêutrons térmicos, comconsequente reação nuclear e liberação de alta transferência de energia linear, por meio de partículas alfa e lítio. Os produtos formados pela reação têm curto alcance e desta maneira, atinge somente as células que incorporam boro. Diversos compostos têm sido estudados, para aumentar a seletividade de captura pelas células tumorais. BNCT atua como uma terapia localizada e com mínimos efeitos colaterais para o tratamento do câncer.

Boron Neutron Capture Therapy (BNCT) is a therapeutic tool for many types of tumor treatment. It is based on administration of a compound which contains the isotope 10 of boron (10B), followed by thermal neutron irradiation and consequent nuclear reaction with release of high linear energy transfer by alpha particles and lithium. The produced products by reaction have a shorter range and thus, they affect only cells with boron inside. Many compounds have been studied to increase the uptake selectivity by tumor cells. BNCT acts as a localized therapy with minimal side effects for cancer treatment.

Boron neutron capture therapy in cancer: past, present and future.

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. 10B is then activated to 11B, which will immediately decay releasing alpha particles and 7Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiforme and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100% of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans.

Boron neutron capture therapy in cancer: past, present and future

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. 10B is then activated to 11B, which will immediately decay releasing alpha particles and 7Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiforme and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100 percent of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans.

O câncer indiferenciado de tiróide (CIT) é um tumor muito agressivo sem tratamento efetivo, uma vez que não capta iodo e não responde à radio ou quimioterapia. O prognóstico desses pacientes é ruim, devido ao rápido crescimento do tumor e surgimento precoce de metástases. A terapia por captura de nêutrons de boro (TCNB) é baseada na captação seletiva de certos compostos de boro não-radioativos pelo tumor, e à subsequente irradiação da área com um feixe de nêutrons apropriado. O 10B é então ativado para 11B, cujo decaimento imediato libera partículas alfa e 7Li, de alta transferência linear de energia (TLE) e alcance limitado. Ensaios clínicos estão sendo conduzidos em pacientes com glioblastoma multiforme e melanoma, e nós estamos explorando sua possível aplicação no CIT. Nossos resultados demonstram que uma linhagem celular do CIT humano mostra captação seletiva de borofenilalanina (BPA) tanto in vitro como após transplante em camundongos "nude". O tratamento de camundongos com TCNB leva a um controle completo do crescimento tumoral e à cura em 100 por cento dos animais. Além disso, cães com CIT espontâneo também apresentam captação seletiva de BPA. No momento, estamos estudando a biodistribuição de BPA em pacientes com CIT, antes de sua aplicação em humanos.