Furusawa, Y., Fukutsu, K., Aoki, M., Itsukaichi, H., Eguchi-Kasai, K., Ohara, H., Yatagai, F., Kanai, T. and Ando, K. Inactivation of Aerobic and Hypoxic Cells from Three Different Cell Lines by Accelerated 3He-, 12C- and 20Ne-Ion Beams. The LET-RBE spectra for cell killing for cultured mammalian cells exposed to accelerated heavy ions were investigated to design a spread-out Bragg peak beam for cancer therapy at HIMAC, National Institute of Radiological Sciences, Chiba, prior to clinical trials. Cells that originated from a human salivary gland tumor (HSG cells) as well as V79 and T1 cells were exposed to 3He-, 12C- and 20Ne-ion beams with an LET ranging from approximately 20–600 keV/μm under both aerobic and hypoxic conditions. Cell survival curves were fitted by equations from the linear-quadratic model and the target model to obtain survival parameters. RBE, OER, α and D0 were analyzed as a function of LET. The RBE increased with LET, reaching a maximum at around 200 keV/μm, then decreased wi...

https://bioone.org/journals/radiation-research/volume-154/issue-5/0033-7587(2000)154[0485:IOAAHC]2.0.CO;2/Inactivation-of-Aerobic-and-Hypoxic-Cells-from-Three-Different-Cell/10.1667/0033-7587(2000)154[0485:IOAAHC]2.0.CO;2.pdf

Inactivation of Aerobic and Hypoxic Cells from Three Different Cell Lines by Accelerated 3He-, 12C- and 20Ne-Ion Beams

THE mechanisms by which mammalian cells are killed by ionising radiation have not been explained at the molecular level and radiations with a high linear energy transfer (LET) can provide an important tool for investing these mechanisms. High-LET radiations, such as neutrons, π-mesons and low-energy heavy ions are known to kill bacteria1,2, yeast3,4, and mammalian cells in vitro5–9 more efficiently per unit dose than radiations with diffuse patterns of ionization, or low-LETs, such as γ or X rays. Other radiobiological phenomena associated with high-LET radiations are a reduced effect of chemical modifiers, for example, oxygen10, on cellular radiation sensitivity and reduction or loss of cellular ability to recover from radiation damage between split radiation doses5,8. Because of these and other attributes, including the favourable depth–dose distribution of heavy ions and π-mesons, high-LET radiations are being actively considered for use in cancer radiation therapy11,12, and a thorough understanding of their biological effects is necessary for them to be used to advantage clinically. We report here that, over an LET range of 1–1953 KeV µm−1, there is an excellent correlation between the efficiency of exponential (single-hit) cell killing and the induction of non-rejoining DNA strand breaks, as measured on alkaline sucrose gradients. This correlation implies that non-rejoined breaks are a cause of cell death.

High-LET radiations induce a large proportion of non-rejoining DNA breaks

The potential of α-particle emitters to treat cancer has been recognized since the early 1900s. Advances in the targeted delivery of radionuclides and radionuclide conjugation chemistry, and the increased availability of α-emitters appropriate for clinical use, have recently led to patient trials of radiopharmaceuticals labeled with α-particle emitters. Although α-emitters have been studied for many decades, their current use in humans for targeted therapy is an important milestone. The objective of this work is to review those aspects of the field that are pertinent to targeted α-particle emitter therapy and to provide guidance and recommendations for human α-particle emitter dosimetry.

https://jnm.snmjournals.org/content/jnumed/51/2/311.full.pdf

MIRD Pamphlet No. 22 (Abridged): Radiobiology and Dosimetry of α-Particle Emitters for Targeted Radionuclide Therapy

Purpose: The LET position of the RBE maximum and its dependence on the cellular repair capacity was determined for carbon ions. Hamster celllines of differing repair capacity were irradiated with monoenergetic carbon ions. RBE values for cell inactivation at different survival levels were determined and the differences in the RBE-LET patterns were compared with the individual sensitivity to photon irradiation of the different cell lines. Material and methods: Three hamster cell lines, the wild-type cell lines V79 and CHO-K1 and the radiosensitive CHO mutant xrs5, were irradiated with carbon ions of different energies (2.4-266.4MeV/u) and LET values (13.7-482.7keV/mum) and inactivation data were measured in comparison to 250kV x-rays. Results: For the repair-proficient cell lines a RBE maximum was found at LET values between 150 and 200keV/mum. For the repair-deficient cell line the RBE failed to show a maximum and decreased continuously for LET values above 100keV/mum. Conclusions: The carbon RBE-LET rela...

RBE for carbon track-segment irradiation in cell lines of differing repair capacity

The clonogenic cell survival assay determines the ability of a cell to proliferate indefinitely, thereby retaining its reproductive ability to form a large colony or a clone. This cell is then said to be clonogenic. A cell survival curve is therefore defined as a relationship between the dose of the agent used to produce an insult and the fraction of cells retaining their ability to reproduce. Although clonogenic cell survival assays were initially described for studying the effects of radiation on cells and have played an essential role in radiobiology, they are now widely used to examine the effects of agents with potential applications in the clinic. These include, in addition to ionizing radiation, chemotherapy agents such as etoposide and cisplatin, antiangiogenic agents such as endostatin and angiostatin, and cytokines and their receptors, either alone or in combination therapy. Survival curves have been generated for many established cell lines growing in culture. One can use cell lines from various origins including humans and rodents; these cells can be neoplastic or normal. Because survival curves have wide application in evaluating the reproductive integrity of different cells, we provide here the steps involved in setting up a typical experiment using an established cell line in culture.

https://www.springer.com/cda/content/document/cda_downloaddocument/9781588293459-c2.pdf?SGWID=0-0-45-387614-p173728605

Clonogenic cell survival assay.

If investigations of the relative biological effectiveness of ionizing radiations with different linear energy transfer are to provide a better insight into certain aspects of radiation-induced damage to biological systems, it is desirable to use as wide a range of radiations as possible. In previous papers results were given of experiments in which the inhibition of clone formation by human cells in tissue culture was studied after various doses of a-, /-, 200-kv X-, and 20-kv X-radiation (1, 2). The present report is concerned with results obtained from cyclotron-accelerated a-particles and deuterons. These particles have LET's between 5 kev/, and 100 kev/u of unit density tissue, and the results to be presented show that in this region the RBE varies rapidly with LET, especially at low levels of damage.

H. M. D. Walter

Papers

Effects of different ionizing radiations on human cells in tissue culture. III. Experiments with cyclotron-accelerated alpha-particles and deuterons.

III. Experiments with Cyclotron-Accelerated Alpha-Particles and Deuterons