Relative Biological Effectiveness (RBE) and Compound Biological Effectiveness (CBE) factors in human melanoma cell lines.

ROSSINI, A E; DAGROSA, MA; CARPANO, M; POZZI, E; THORP, S; CASAL, M; JUVENAL, GJ; PISAREV, MA

Mainz, Alemania

Otro; Young Researchers BNCT Meeting,; 2009

Unversität Mainz, Alemania

Despite the fact that many tumors are similar from the histologic point of view, it is a common experience that their radiosensitivity may be different. Therefore it is important to know the radiobiological characteristics of each tumor in order to improve The therapeutic effectiveness of BNCT. This is one of the aims of the present studies. Since the development of a mixed thermal and epithermal –named hyperthermal- neutron beam at the RA-6 reactor of the National Comission of Atomic Energy (CNEA) in Argentina, and the approvement of a protocol to evaluate the efficacy of Boron Neutron Capture Teraphy (BNCT) for cutaneous skin melanomas in extremities, the task of calculating a “clinical” relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors have been of particular importance to the improvement of the therapeutic ratio (tumor dose/normal tissue dose). We determined the CBE values for p-Borophenylalanine (BPA) and RBE values of the neutron beam on three in vitro models: three different human melanoma cell lines: M8, A375 and Mel-J. The cells were irradiated in the thermal neutron beam of the RA-3 reactor (CNEA Buenos Aires). Surviving fraction (S.F) was studied as the endpoint from clonogenic assays. Either the RBE of the beam and the CBEs for p-BPA were determined for two different endpoints. At S.F of 0,3 and S.F of 0,07, (30% and 7% of survival respectively). The results for the three cell lines M8, A375 and Mel-J respectively were: beam RBE0,3: 1,39; 1,58 and 1,9. Beam RBE0,07: 1,35; 1,53 and 1,59. CBEs 0,3 : 2,6; 2,75 and 4,2. CBEs 0,07: 2,3; 2,37 and 3,28. The CBE for p-BPA is related, in vitro (cell cultures), basically to the ratio: BPAt concentration in tumor/BPAs concentration in normal skin (accumulation ratios) and related to biodistribution of BPA at subcellular level (distance from nucleus and intracellular localization). The individual characteristics of the cell lines are very important too. Cellular size, nucleous size and expression levels of the amino acid transporters implicated in the p-BPA captation will be critical parameters that should influence the CBEs values. For example the tumor cells with their large nucleus/cytoplasm ratio would be more damaged, providing a higher therapeutic benefit. At first sight, the most remarchable results are the CBEs values for Mel-J cell line, providing a dose therapeutic benefit of almost 4 to 1 (in comparisson with the conventional gamma dose). For the other two cell lines the results are similar. More solid conclussions will be discussed when we have results from the analysis of this kind of cellular characteristics (ultraestructure characterization of the cells) and definitive results of the captation assays. Nevertheless some previous results (not showed) tell us that Mel-J is one of the cell lines that transport BPA more actively.   These are the first measured data for RBE and CBEs for human melanoma cell lines and should be usefull for the optimization of the dosimetric analysis for the treatment of cutaneous melanomas with BNCT in Argentina.