Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation

Abstract

Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation irradiation

FLASH radiotherapy with photon beams

“…showed that a dose of 2 Gy delivered with SBBR at an instantaneous dose rate of 50 Gy/s to 9 L rat glioma cells resulted in a surviving fraction (SF2) of 32% compared to 74% when delivered with an orthovoltage field at 0.0127 Gy/s. Similar results were later reproduced on the same cell line after a single dose of 8 Gy at an instantaneous dose rate of 46 Gy/s 60 . Moreover, a further increase in the SBBR instantaneous dose rate above 200 Gy/s led to fourfold increase in the dose rate enhancement ratio measure for 10% clonogenic survival 43 .…”

“…Interestingly, when the same irradiation modalities were used to irradiate Madin‐Darby Canine Kidney MDCK nontumor cells, both SBBR and conventional dose rate X‐ray irradiation showed similar SF2 between 31% and 38% 59 . In the same publication, Li et al 60 . conclude that the radiosensitizing effect of BI 6227, a Polo kinase 1 inhibitor, is likely to be dose rate dependent.…”

“…43 Interestingly, when the same irradiation modalities were used to irradiate Madin-Darby Canine Kidney MDCK nontumor cells, both SBBR and conventional dose rate X-ray irradiation showed similar SF2 between 31% and 38%. 59 In the same publication, Li et al 60 conclude that the radiosensitizing effect of BI 6227, a Polo kinase 1 inhibitor, is likely to be dose rate dependent. This inhibitor combined to 8 Gy single dose irradiation significantly decreased the survival fraction of 9 L glioma cells by 2.6% when the irradiation was performed with an orthovoltage field at 0.0127 Gy/s, and by 4.2% when performed with SBBR at an instantaneous dose rate of 46 Gy/s.…”

“…Such a 60 Co source of approximately 1.2 cm 3 in size, assuming pure 60 Co, could theoretically be used for UHDR irradiations of small animals to depths of ∼3 cm. However, the mean 60 Co gamma energy of 1.25 MeV would pose significant engineering challenges in terms of appropriate radiation shielding and a complex irradiation system would have to be designed to achieve sub-second irradiations. Another possible radioisotope-based UHDR delivery could be achieved with a low-energy brachytherapy seed of high activity.…”

“…A combination of a number of 20 Ci 192 Ir seeds could potentially result in UHDRs at shallow depths in tissue. The mean energy of a 192 Ir source of 360 keV means that a less complex shielding mechanism would be necessary compared to the 60 Co source; however, UHDR will only be achieved at shallow depths of <1 mm and the utility of such source would be rather limited. From the previous text, it follows that radioactive source arrays could possibly be used for UHDR skin treatments.…”