Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Intratumor heterogeneous distribution of boron-10 compound for neutron capture therapy, based on radiobiological findings from in vivo mouse studies

S Masunaga MD PhD 1, K Ono MD PhD 1, Y Sakurai PhD 2, M Takagaki MD PhD 1, M Suzuki MD 3, T Kobayashi PhD 2, Y Kinashi MD PhD 1

1 Radiation Oncology Research Laboratory and, 2 Div Radiation Life Science, Research Reactor Institute, Kyoto University,, 3 Dept Radiology, Kinki University School of Medicine; Osaka, Japan,

AIMS: To examine distribution status of 10B-compound for neutron capture therapy within solid tumors radiobiologically. METHODS: After continuous labeling with or without BrdU, SCC VII tumor-bearing mice received one of the following treatments; 1) tumor excision right after thermal neutron irradiation following widely employed 10B-compound, sodium borocaptate-10B (BSH) or p-boronophenylalanine-10B (BPA) administration, 2) tumor excision 5 min through 72 h after thermal neutron or gamma-ray irradiation, 3) determination of hypoxic fraction by gamma-ray test irradiation 5 min through 72 h after thermal neutron or gamma-ray irradiation, 4) determination of the sensitivity to gamma-rays 0 - 24 h after thermal neutron or gamma-ray irradiation. RESULTS: 1) BSH and BPA sensitized quiescent (Q) and total (proliferating (P) + Q) tumor cells, respectively, and the use of 10B-compound, especially BPA, widened the sensitivity difference between Q and total cells. 2) The use of 10B-compound, especially BPA, increased the repair capacity from potentially lethal damage (PLDR) and induced PLDR pattern like post-gamma-ray irradiation. 3) Reoxygenation after thermal neutron irradiation following 10B-compound, especially BPA, administration occurred slowly, compared with after neutron irradiation only and looked like after gamma-ray irradiation. 4) The use of 10B-compound, especially BPA, promoted sublethal damage repair in total cells and the recruitment from Q to P state, compared with after thermal neutron irradiation only. CONCLUSION: All these findings suggested the difficulty in distribution of 10B-compound, especially BPA, in Q cells and the heterogeneity in intratumor 10B-compound distribution.

KEY WORDS: Boron neutron capture therapy, Quiescent cell, Solid tumor, 10B-compound.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on novel therapies.