Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy

Abstract

Abstract. Purpose: The purpose of this study was to identify combinations of dose rate and exposure time that have the potential to provide curative treatment with targeted radionuclide therapy applying low dose rate beta irradiation. Methods: Five tumour cell lines, U-373MG and U-118MG gliomas, HT-29 colon carcinoma, A-431 cervical squamous carcinoma and SKBR-3 breast cancer, were used. An experimental model with 10 5 tumour cells in each sample was irradiated with low dose rate beta particles. The criterion for successful treatment was absence of recovery of cells during a follow-up period of 3 months. The initial dose rates were in the range 0.1-0.8 Gy/h, and the cells were continuously exposed for 1, 3 or 7 days. These combinations covered dose rates and doses achievable in targeted radionuclide therapy. Results: Continuous irradiation with dose rates of 0.2-0.3 and 0.4-0.6 Gy/h for 7 and 3 days, respectively, could kill all cells in each tumour cell sample. These treatments gave total radiation doses of 30-40 Gy. However, when exposed for just 24 h with about 0.8 Gy/h, only the SKBR-3 cells were successfully treated; all the other cell types recovered. There were large cell type-dependent variations in the growth delay patterns for the cultures that recovered. The U-118MG cells were most resistant and the U-373MG and SKBR-3 cells most sensitive to the treatments. The HT-29 and A-431 cells were intermediate. Conclusion:The results serve as a guideline for the combinations of dose rate and exposure time necessary to kill tumour cells when applying low dose rate beta irradiation. The shift from recovery to "cure" fell within a narrow range of dose rate and exposure time combinations.

γH2AX and cleaved PARP-1 as apoptotic markers in irradiated breast cancer BT474 cellular spheroids

“…Analysis of radiation-induced apoptosis is of interest for studies of death effects due to the daily radiation doses of 2 Gy that most often is given in conventional radiation therapy (11,12) and also after therapy with radionuclides with low dose rate (13)(14)(15).…”

THE ENERGY DEPOSITION DISTRIBUTION AT THE MICRO AND NANO-SCALE FOR MOLECULAR TARGETED RADIOTHERAPY: COMPARISON BETWEEN 125I, 99MTc AND 64Cu

“…It was reported, for example, that a higher dose rate delivered could be beneficial to efficiently killing tumor cells [17,18]. It is also worth to say that the dose rate in radionuclide therapy is at least two orders of magnitude lower than in external radiotherapy [19]. Nevertheless, the effect of the dose rate on the cellular cytotoxicity is beyond the scope of this study.…”

Clinical radionuclide therapy dosimetry: the quest for the “Holy Gray”

“…It should be noted that late-responding normal tissues and slow-growing tumours allow easier modelling than early-responding normal tissues and fast-growing tumours because of repopulation during treatment in the latter. Nevertheless, this may be regarded as a major development, stimulating further research [108] aimed towards the creation of a firm fundamental basis for radionuclide radiotoxicity and radiodosimetry. In future, it looks as if we shall no longer be looking at a “Holy Gray”, but rather at the worldly “BEGray”.…”