ESTRO 36 Abstract Book

S487 ESTRO 36 _______________________________________________________________________________________________

adjusted and thresholded to create a binary 3D vessel map (VM). Hoechst-negative vessels were excluded from the VM. These VMs were used to simulate 3D oxygen distributions based on a Michaelis-Menten relation. An average input function (AIF) was determined by fitting activities in the left ventricles over 4 mice to derive mean parameters. Based on oxygen distribution and AIF, FMISO retention was simulated on the same VMs. FMISO-positive regions of 3x3mm2 in the tumor center in 5 random sections were compared against manually contoured pimo-positive regions to validate the simulation by determining hypoxic fraction (HF) and overlap ratio. Necrosis was excluded based on H/E staining on the same sections. To compare 3D and 2D simulations, the simulations and analysis were repeated in 2D. Parameters for all simulations were set to commonly used values (Mönnich et al., 2011).

PO-0887 Experimental validation of a 3D model to simulate FMISO spatial retention in HNSCC tumor xenografts L.J.M. Wack 1 , A. Menegakis 2 , R. Winter 1 , S. Boeke 2 , K. Trautmann 3 , A. Leun 1 , M. Krueger 4 , B. Pichler 4 , D. Mönnich 1 , D. Zips 2 , D. Thorwarth 1 1 Clinic for Radiation Oncology- University Hospital Tübingen, Section for Biomedical Physics, Tübinge n, Germany 2 University Hospital Tübingen, Department of Radiation Oncology, Tübingen, Germany 3 University Hospital Tübingen, Department of Pathology and Neuropathology, Tübingen, Germany 4 Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Tübingen, Germany Purpose or Objective Tumor hypoxia is prognostic for poor outcome after radiotherapy (RT). A method for non-invasi ve assessment of hypoxia is PET using hypoxia radiotracers such as FMISO. For this study, we evaluated a tool to simulate 2D and 3D FMISO accumulation on realistic vessel architectures, which can be compared against experimental pimonidazole (pimo) stainings of the same tumor. Material and Methods Dynamic PET/MR imaging was performed in FaDu tumors (human HNSCC) grown in the right hind leg of nude mice for about 5 weeks, using an injected FMISO activity of ~12MBq. Pimo and hoechst 33342 were injected 1h and 1min prior to tumor excision, respectively, to allow staining for tumor hypoxia and perfusion status of blood vessels. After excision, two tumors were snap frozen and the central part was cut into 120 consecutive sections of 10µm. Immunofluorescence staining was performed for pimo and endothelial marker CD31. Sections were subsequently scanned on a Zeiss Axiovert fluorescence microscope to detect pimo, CD31 and hoechst. The fluorescence images were rigidly registered, manually

Results Differences in experimental and 3D-simulated hypoxic fractions (HF) were not significant, while differences between experimental and 2D-simulated HF was significantly different for Tumor 2 (p=0.02, cf. Table). 3D simulations matched much better with pimo distribution than 2D simulations only. The true-positive rate was increased about 0.2 for both tumors, the true- negative rate by about 0.08 for 3D simulations when compared to 2D. 56% of 3D-simulated FMISO-positive voxels were located within pimo-positive areas, while another 14% were located within 50µm distance, as to 37% and 8% for 2D, respectively (cf Table, Figure). Conclusion When performing hypoxia tracer simulations on actual VMs, 3D models accounting for out-of-plane diffusion must be used to obtain realistic results. In a 3D vascular model, spatial tracer distributions similar to those observed in vivo can be simulated. Hence, 3D FMISO simulation on