Theranostic applications of pair-production for enhancing radiation therapy.
Isrow D, Brown SL, and Kim JH. Theranostic applications of pair-production for enhancing radiation therapy. Int J Radiat Oncol Biol Phys 2017; 99(2):E672-E673.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): To enhance radiotherapy by utilizing pair-production, the probability of which increases with X-ray energy and atomic Z number. Introducing high Z metals during 18MV irradiation should result in increased cell killing compared to 18MV irradiation without metal or 6MV with/without metal. This effect will be due to increased pair-production near high Z nuclei which increases locally absorbed radiation dose. This effect requires metal, preferably nontoxic, to be present during irradiation and will be measured in vitro with clonogenic survival assays. Purpose/Objective(s): Clonogenic survival assays were carried out using A549 human lung cancer cells. Tissue culture plates were irradiated with 2Gy of either 6MV or 18MV photons with or without metal drugs (100 uM sodium phosphotungstate hydrate, 4ug/ml cisplain, and 12ug/ml carboplatin) present during radiotherapy. Metal drugs were introduced to culture media 2 hours prior to irradiation and left in place during irradiation. The media was replaced immediately after irradiation with metal-free media. Calibrated output factors were used to ensure the same absorbed dose between the two beam energies under identical experimental setup conditions. Results: Mean plating efficiency was determined to be 41% on average for A549. Incubating cells in 100uM tungsten for 4 hours without irradiation produced no significant toxicity (>95% survival). In the absence of metal drug, the 2Gy 6MV and 18MV plates showed similar survival (64% vs 67%). When tungsten compound was introduced, the 6MV plate again showed 66% survival, however the 18MV plate showed 34% survival, approximately double cell killing. These experiments were repeated at 4, 6, and 8Gy to generate cell survival curves and the radiation sensitization enhancement ratio (SER) was found to be approximately 1.5. The tungsten 18MV survival curve shows a minimal shoulder region compared to the 6MV with/without tungsten and 18MV without tungsten curves, suggesting inhibition of sublethal damage repair. The 2Gy 6MV vs 18MV clonogenic survival studies were carried out for 4ug/ml cisplatin and 12ug/ml carboplatin which similarly showed approximately 40% enhancement of cell killing for both drugs at 18MV compared to 6MV. Conclusion: Cells treated with 18MV irradiation in the presence of 100uM sodium phosphotungstate hydrate showed approximately 50% less cell survival at 2, 4, 6, and 8Gy compared to 6MV with/without metal and 18MV without metal. Cisplatin and carboplatin show similar radiosensitization at 18MV yielding 40% more cell killing than 6MV. This effect is due to pair-production leading to increased photon-matter interaction and requires metal to be present at time of irradiation. The survival curves at 2, 4, 6, and 8Gy show loss of initial shoulder region suggesting impaired sublethal damage repair or increased effective LET. The generation of 511keV annihilation photons in situ may allow tumor imaging and dose measurement via PET technology. Confirmatory in vivo studies are planned.