RESUMO
PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.
Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Pulmonares/radioterapia , Animais , Argentina , Boro/farmacocinética , Boro/uso terapêutico , Compostos de Boro/farmacocinética , Terapia por Captura de Nêutron de Boro/instrumentação , Estudos de Viabilidade , Frutose/análogos & derivados , Frutose/farmacocinética , Humanos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Neoplasias Pulmonares/metabolismo , Modelos Animais , Modelos Biológicos , Fótons , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Ovinos , Fatores de Tempo , Distribuição TecidualRESUMO
The quantification and analysis of the tracks forming the autoradiography image of a tissue section is essential for the measurement of particle emitter concentration and distribution (e.g. (10)B) in the sample. Conventional counting techniques cannot be used when track density is high because of track overlapping. A densitometry supported by image analysis method suitable for these cases has been developed. Optical density measurements obtained for boron solutions of known concentrations showed a linear behavior in the range of concentrations under consideration.
RESUMO
The amount of (10)B in tissue samples may be determined by measuring the track density in the autoradiography image produced on a nuclear track detector. Different systems were evaluated as reference standards to be used for a quantitative evaluation of boron concentration. The obtained calibration curves were applied to evaluate the concentration of (10)B in melanoma tumour of NIH nude mice after a biodistribution study. The histological features observed in the tissue sections were accurately reproduced by the autoradiography images.
Assuntos
Autorradiografia/métodos , Boro/farmacocinética , Modelos Animais de Doenças , Melanoma Experimental/metabolismo , Animais , Calibragem , Feminino , Camundongos , Camundongos Nus , Distribuição TecidualRESUMO
A prospective study was undertaken to assess the radiotoxicity of accelerated particles in pulmonary alveolar macrophages (AM). We evaluated the effects of a single dose (10-75 Gy) of an external low-energy (20 MeV) proton beam on cultured AM oxidative metabolism and phagocytic function. Macrophages are the first line of defense against invading pathogens and are known to generate superoxide anion (O2), nitric oxide (NO), and mediators of antimicrobial and antitumoral defense mechanisms. We obtained AM by bronchoalveolar lavage from young (1-2 month old) and aged (9-12 month old) male Wistar rats. Cell viability, phagocytosis, O2 and NO production in control and proton-irradiated cultured AM were evaluated The effect of proton irradiation on cell viability was dose-dependent The higher doses induced a dramatic decrease in viability in the aged population. Phagocytosis increased 1.3-1.4 fold inboth populations irrespective of the dose delivered. Generation of O2 was always higher in the aged population for all the doses assayed and showed no significant variation from the control values. In the young population a clear increase was observed with doses of 25 and 50 Gy. NO production in AM from young animals rose in a dose-dependent manner. Conversely, proton irradiation did not affect NO production in macrophages from aged animals. The results of this study demonstrate that AM isolated from young and aged rats are functionally different and show a distinct behavior when exposed to proton irradiation. These findings suggest that age may condition response and must be taken into account when accelerated particle-radiotherapy protocols are considered as a valid therapeutic option for the treatment of cancer. To the best of our knowledge, this is the first report comparing sham-irradiated and proton-irradiated young and aged AM.
Assuntos
Envelhecimento/fisiologia , Macrófagos Alveolares/efeitos da radiação , Prótons , Animais , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Óxido Nítrico/metabolismo , Fagocitose/efeitos da radiação , Ratos , Ratos Wistar , Superóxidos/metabolismoRESUMO
We evaluated the in vivo response to heavy particle irradiation in rat tail epidermis using silver-stained nucleolar organizer regions (AgNOR) as the end-point. The energy degradation of the beam across the circular section of the tail allowed us to study the damage elicited by two different LET regions of a helium beam, i.e. non-Bragg peak (NBP) and Bragg peak (BP), at different sites on the same sample. The tails were locally irradiated with a helium ion beam at different fluences. AgNOR exhibited marked variations between tissue areas only a few micrometers apart within each tail exposed to a given beam fluence. An analysis of the AgNOR variations in NBP and BP areas of tails exposed to different beam fluences revealed a dose-dependent effect. The AgNOR provide quantitative evidence of differential damage in neighboring tissue areas exposed to different LET regions of a helium-ion beam.
Assuntos
Hélio , Íons , Transferência Linear de Energia , Animais , Relação Dose-Resposta à Radiação , Epiderme/efeitos da radiação , Íons Pesados , Modelos Lineares , Região Organizadora do Nucléolo/efeitos da radiação , Radioterapia de Alta Energia/instrumentação , Ratos , Ratos Wistar , Coloração pela Prata , Cauda/efeitos da radiaçãoRESUMO
This study presents new evidence as to the usefulness of ultrasound scanning in field conditions, to screen out hydatidosis in endemic areas, and to compare its detection capability with serological methods. It also intends to demonstrate that for an efficient rural ultrasound screening, neither an experienced ultra sonographer nor expensive and sophisticated equipment is necessary, it can be done by suitably trained personnel (eg, nurse, public health worker), using basic equipment, without public health installations or electricity, thus making it a feasible, simple, fast, and cheap screening method for hydatidosis.