Abstract Book

S1277

ESTRO 37

Results For A375 cells, cell viability for 0, 2, 4, 8, 16 and 24 Gy for the 96-well IMRT plan were 2.08, 1.75, 1.42, 0.76, 0.55, 0.55, and with open-field, homogeneous irradiations they were 2.08, 1.65, 1.18, 0.65, 0.52, 0.5. These differences were not statistically significant (p = .82, unpaired t-test) ( Figure 1, a ). The corresponding values for LN18 cells were 2.01, 1.7, 1.39, 0.77, 0.27, 0.25 and 1.91, 1.65, 1.33, 0.66, 0.35, 0.37 respectively, and again these differences did not reach statistical significance (p = .95, unpaired t-test) ( Figure 1, b ).

EP-2313 Magnetic nanoparticle mediated in-vitro radiosensitization at megavoltage radiation energies

Abstract withdrawn

EP-2314 Novel RG108-derived DNA-methyltransferase inhibitor as a radiosensitizer in glioblastoma cells C.W. Wee 1 , J.H. Kim 1 , H.J. Kim 1 , S.Y. Suh 1 , H.C. Kang 1 , B.S. Shin 2 , E. Ma 3 , I.H. Kim 1 1 Seoul National University Hospital, Department of Radiation Oncology, Seoul, Korea Republic of 2 Sungkyunkwan University, School of Pharmacy, Suwon-si, Korea Republic of 3 Catholic University of Daegu, College of Pharmacy, Gyeongsan-si, Korea Republic of Purpose or Objective The prognosis of glioblastoma (GBM) is dismal despite radiotherapy and temozolomide, and therefore, novel radiosensitizers to enhance the therapeutic ratio are necessary. This study aimed for the synthesis of a novel DNA-methyltransferase inhibitor (DNMTi) that radiosensitize glioblastoma cells and possess biostability. Material and Methods A novel non-nucleoside heterodimer, designated as compound MA17, was derived from RG108 which is a commercially available DNMTi. Three human GBM cell lines (U373MG, U87MG, and T98G) and normal human astrocytes (NHAs) were screened for the radiosensitizing effects of MA17. Clonogenic assays were performed in triplets to measure cell lethality, and sensitizer enhancement ratios (SERs) at survival fraction of 0.5 were obtained to quantify the radiosensitizing effect of MA17 in each cell line. Quantitative assays of DNMT1 inhibition was performed. Pharmacokinetic characteristics were examined in mice (n=4) at a concentration of 10 mg/kg. Results MA17 significantly radiosensitized U373MG, U87MG, and T98G with mean SERs of 1.896, 1.312, and 1.331, respectively (all p <0.05 by ratio paired t-test) (Fig. 1). However, MA17 did not affect the radiation lethality in NHAs with mean SER of 0.960 (95% confidence interval, 0.897–1.023; p =0.193). MA17 also inhibited the activity of DNMT1 by 60.29±28.22%. The mean half-life of MA17 in vivo was 1.0±0.2 hour. Conclusion A novel DNMTi, MA17, significantly enhances cell lethality of radiation in GBM cells without affecting the radiation response in NHAs. Biostability of MA17 was also proven with a long half-life in vivo . In vivo studies for MA17 using a xenograft mouse model are ongoing. EP-2315 Tumor IGF-1 and insulin receptor expression and its linkage to anti-receptor treatment response A. Iversen 1 , M. Vendelbo 2 , N. Jessen 3 , J. Frøkiær 4 , A. Morsing 5 , M. Busk 1 1 Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C, Denmark 2 Aarhus University Hospital, Department of Nuclear Medicine and PET Center, Aarhus C, Denmark 3 Aarhus University, Department of Clinical Medicine, Aarhus, Denmark 4 Aarhus University Hospital, Department of Nuclear Medicine and PET-Center, Aarhus C, Denmark 5 Aarhus University Hospital, Department of Nuclear Medicine and PET Centre, Aarhus C, Denmark

The clonogenic assays showed that the colony numbers for A375 cells with the 6-well IMRT plan for 0, 2, 4, 8, 16 and 24 Gy were 208, 141, 74, 0, 0, 0 and for the open- field homogeneous irradiations they were 194, 143, 55, 0, 0, 0. These differences did not reach statistical significance (p = .92, unpaired t-test) ( Figure 2, a & b ). The quantitative γ-H2AX analysis showed a radiation dose dependant increase in γ-H2AX signal intensity. Mean relative γ-H2AX signal intensity (normalised to the cell number) for 0, 2, 4, 8, 16 and 24 Gy with the 96-well IMRT plan were 4.74, 11.74, 18.68, 32.63, 60.51, 88.40 and the corresponding values for open-field, homogeneous irradiations were 7.15, 16.33, 23.83, 41.35, 64.3 and 102.7. These differences were not statistically significant (p = .75 unpaired t-test) ( Figure 2, c & d ).

Conclusion We have validated a high-throughput, in-vitro radiobiology platform by comparing three relevant and important biological parameters to conventional open- field irradiations. This platform is now in routine use for radiobiology experiments within our Institute. References 1 A high-throughput in-vitro platform for radiobiology experiments; National Cancer Research Institute Cancer Conference, November 2017, Liverpool, UK, Abstract ID: 849

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