ESTRO 2021 Abstract Book

S1641

ESTRO 2021

Variance (GLV) had a strong correlations (R>0.7) with West-24 gene signature score (R=0.73) and expression of 4 individual genes: COL5A1 (R=0.76), ITGA5 (R=0.73), TGFB1 (R=0.87) and PDLIM2 (0.73). The distribution of GLV was greater in tumour bed than bladder wall (Fig 1). While Large Area High Gray Level Emphasis (LAHGLE) correlated with SLC16A1 expression (R=0.71), the interquartile range of distribution of this feature in tumour bed and bladder wall overlaps and hence is unlikely to reflect differences in tumour biology.

Conclusion This pilot study identified a potential radiomic feature as a surrogate for gene expression, thereby allowing a non-invasive method of assessing for prognostic and predictive biomarkers. Further validation in a larger cohort would be worthwhile.

PO-1925 In vitro characterisation of the bacteria-derived hypoxia-selective cytotoxin BE-43547 M. Busk 1 , P. Eggertsen 1 , J. Overgaard 1 , M.R. Horsman 1 , K.M. Jacobsen 2 , T. Tørring 3 , T.B. Poulsen 2

1 Aarhus University Hospital, Experimental Clinical Oncology, Aarhus, Denmark; 2 Aarhus University, Department of Chemistry, Aarhus, Denmark; 3 Aarhus University, Department of Engineering—Microbial Biosynthesis, Aarhus, Denmark

Purpose or Objective Hypoxia-activated pro-drugs like Tirapazamine and the second-generation drug TH-302 have received considerable attention. However, highly variable levels of cellular nitroreductases in tumor tissue, which are required for drug activation, poses a limitation. Thus, novel drugs that selectively targets hypoxic tumor cells independently of nitroreductase activity may be beneficial. BE-43547 which is produced by bacteria in hypoxic niches, possible to kill competing microorganisms, shows selective cytotoxicity against hypoxic cells by an unknown working mechanism. The overall purpose of this study was to characterize the in vitro potency and hypoxia-selectivity of BE-43547 and, when relevant, compare it to TH-302. Materials and Methods A panel of cell lines consisting of 2 squamous cell carcinomas (FaDu DD and SiHa) and 2 adenocarcinomas (MDAMB-231 and DU145) were grown in monolayers and exposed to normoxia (20% O 2) , chronic (24h) hypoxia (0.5% O 2 ) or anoxia (0%) or acute (4h) anoxia in the absence/presence of BE-43547, and the half maximal inhibitory concentration (IC 50 ) values and the hypoxia-cytotoxicity-ratio (HCR) were determined from clonogenic survival assays. As a comparison, TH-302 was tested under chronic anoxia in FaDu DD , SiHa and MDAMB-231 cells. Finally, to mimic tissue penetrability barriers, both drugs were tested in ~650 µm FaDu DD spheroids exposed to 20 or 0% O 2 for 24h in the absence/presence of drugs, followed by trypsination and assessment of clonogenic survival. Results BE-43547 showed no inter-cell line variability and was highly potent with normoxic and anoxic IC 50 values of ~400 nM and ~5 nM respectively, and a HCR of ~85. HCR dropped to ~20 at 0.5% O 2 . Reducing the drug exposure time to 4h decreased HCR 3-fold, mainly through an increase in anoxic IC 50 . Hypoxia selectivity was maintained regardless whether drug was added prior to or during the hypoxic challenge. For comparison TH-302 showed significant variability in IC 50 values, especially under oxic conditions where a nearly 10-fold difference between the most (FaDu DD ) and least (SiHa) sensitive cell line was