Comparative study of boron uptake by different tissues, main focus in calcified tissues, administrated as boric acid and boronophenylalanine in high doses

OLIVERA MS; BRANDIZZI D; CARPANO M,; DAGROSA MA; PORTU A; CABRINI R

MISSOURI, COLUMBIA

Congreso; The 17th International Congress on Neutron Capture Therapy; 2016

International Society for Neutron Capture Therapy

Several boron compounds have been studied for your application in BNCT (Boron Neutron Capture Therapy), as treatment for differents types of tumors, where the uptake of 10B by tumoral tissue is of great relevance. Boric acid (BA) was used in the origin of this therapy for brain tumors treatment. Knowing the favorable relation between B and bone, we have started to study the biodistribution of B administered as boric acid in this tissue, in differents doses and administration times, such that we get to define a proper dose for the application in BNCT, as well as to know more about of your location in the oseo tissue since, at date, there is a few studies about this matter. Chou and coworkers have reported the results of biodistribution of BA and others boronated compounds, but administered in menor doses that used in this work.Our study focuses especially on calcified tissues, in view of potential treatment for certain bone tumors, e.g. those which have sectors undergoing bone formation, such as osteoblastic sarcoma. Osteosarcoma is the most common type of bone cancer in children and adolescents, especially between 10 and 19 years old. The most widely used boronated compound in clinical therapy is a D-fructose / L-p-boronophenylalanine (BPA) complex, thence our interest in comparative study.In previous studies, we found high concentrations of B in calcified tissues when animals were infused with a solution of boric acid (BA). The aim of this study was to analyze boron uptake in these tissues and other metabolically important tissues by administrating boron in comparative doses in the form of two different compounds: BA and BPA, in doses of 40 mg B/ BW of animal. We found large quantities of boron in diaphysis and epiphysis of normal Wistar rats, in the order of 200 ppm for Group 200 BA, administered with 200 mg B/BW of animal. A bone tissue/liver (or kidney) ratio of about 2.5 and bone tissue/skin ratio of 2 - 3 were found for Groups 200 and 40 BA. For animals infused with BPA solution, Group 40 BPA had bone tissue/ liver and bone tissue/skin ratios equal to or lower than 1. The bone tissue/skin ratio for animals infused witht BA is seven times greater than the bone tissue/skin ratio for BPA animals infused. This results were obtained 3 hs post i.p. infusion. On the other hand, the skin, kidney and muscle are the tissue with upper uptake of BPA at this time. The boric acid seem have more affinity by mineral tissue than organic tissue (soft tissue) improving notably the ratio between interest organs such as the skin which is dose limiting. The data obtained are particularly important to both the therapeutic approach and the radiotoxic approach in BNCT treatment of bone tumors.