RESPONSES OF TOTAL AND QUIESCENT CELL-POPULATIONS IN SOLID TUMORS TO BORON AND GADOLINIUM NEUTRON-CAPTURE REACTION USING NEUTRONS WITH 2 DIFFERENT ENERGY-SPECTRA

In neutron capture therapy, whose effectiveness depends on the tumor d istribution of neutron capture compound and the neutron energy distrib ution, controlling quiescent tumor cells with clonogenic potential is critical for therapeutic gain, as is the case in conventional radio- a nd chemotherapy, Tumor-bearing mice were continuously given 5-bromo-2' -deoxyuridine (BrdU) to label all proliferating cells, After administr ation of sodium borocaptate-B-10 (BSH), dl-p-boronophenylalanine-B-10 (BPA) or gadodiamide hydrate (Omniscan), the tumors were irradiated wi th neutrons of different cadmium (Cd) ratio, and then isolated and inc ubated with cytochalasin-B (a cytokinesis blocker), The micronucleus ( MN) frequency in cells without BrdU labeling (quiescent cells) was det ermined using immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU, Without drug s, quiescent cells showed lower MN frequencies than total cells, but n eutron irradiation reduced gamma-ray sensitivity difference between th e two, Relative biological effectiveness (RBE) of neutrons compared wi th gamma-rays was greater in quiescent cells than in total cells, and low Cd ratio neutrons tended to exhibit large RBE values, With neutron capture compounds, MN frequency for each cell population was increase d, especially when high Cd ratio neutrons were used; BPA increased the MN frequency for total cells to a greater extent than BSH, However, t he sensitivity of quiescent cells treated with BPA was lower than that in BSH-treated quiescent cells, This tendency was clearly observed in high Cd ratio neutrons, Omniscan only slightly increased the MN frequ ency in both cell populations, compared with irradiation alone, withou t drugs, From the viewpoint of increasing the quiescent cell sensitivi ty, tumors should be irradiated with high Cd ratio neutrons after BSH administration.