Basic research for Gd-NCT

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The current BNCT can not destroy the tumor cells which don't take up boron because alpha particle is too short for strilizing neighbor cells. To break this limitation, we studied the possibility of Gd-NCT using Gd-DTPA.The cell killing effect of Gd-NCT examined in cultured SCCVII tumor cells presented the inferior effect to that of BNCT at all drug cncentrations ; 2,3 and 5 mM.Especially, the cell survival curve at 2 mM has shoulder. In vivo system, Gd-NCT showed maximum effect 2-3 min after the injection of Gd-DTPA, when the effect was asessed by cytokinesis blocked micronucleus assay. In colony formation assay, Gd^<157>N-DTPA(0.6 mu mole/g mouse body weight) yielded the effect being similar to that of B^<10>NPA(750 mg/g, average B^<10>N concentration in tumors = 0.7mu mole/g). We previously elucidated that alpha component of cell survival curve completely appreared as the fraction of cells with normal nuclear division (NNDF) ; without micronucleus appearance nor uneven nuclear division. Since the cell survival curve of SCCVII tumors following Gd-NCT is linear, the homogeneity of B^<10>N distribution at cellular level can be investigated by comparing cell survival curve and NNDF curve. The NNDF curve showed precise agreement with the cell survival curve following Gd-NCT ; -lnNNDF=0.137・T(m) vs.-lnSF=0.131・T(m). In BPA-NCT, however, two curves showed a discrepancy. These findings mean that Gd-DTPA distributed more homogeneously than BPA.