ESTRO 37 Abstract book

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ESTRO 37

hours after the second application of ITPP was optimal for maximal tumor reoxygenation. Interestingly, ITPP alone did not affect the growth of tumor xenografts but significantly sensitized the tumor to IR. Immunohistochemical analysis of γH2AX foci demonstrated increased DNA damage within hypoxic tumor regions after combined treatment of ITPP/IR as compared to IR alone. Furthermore, IR-induced tumor hypoxia observed at 4 days after IR was associated with a decrease in tumor vascular density and pericyte coverage, which was prevented by combinatorial treatment with ITPP. This difference in tumor hypoxia 4 days after IR could be exploited by a second fraction of 10 Gy and resulted in a sustained delay of tumor growth in ITPP/IR treated mice. Moreover, ITPP prevented a decrease of vascular density even after two fractions of 10 Gy. Conclusion ITPP administration induces an immediate increase of oxygen availability that can be exploited by a combined treatment modality with IR as shown in our HNSCC and NSCLC tumor models. ITPP seems to protect the tumor vasculature upon IR, which may positively influence the hypoxia status. Overall, our results support the strong rationale to combine ITPP with hypofractionated radiotherapy for hypoxic tumors. OC-0266 Quantitative assessment of CAIX expression with SPECT imaging in head and neck cancer xenografts F. Huizing 1 , B.A.W. Hoeben 1 , G. Franssen 2 , O. Boerman 2 , S. Heskamp 2 , J. Bussink 1 1 UMC St Radboud Nijmegen, Radiation oncology, Nijmegen, The Netherlands 2 UMC St Radboud Nijmegen, Nuclear Medicine, Nijmegen, The Netherlands Purpose or Objective Tumor hypoxia forms a major cause of radio- and chemotherapy resistance in solid tumors. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker strongly associated with poor outcome, which makes it an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment combined with radiotherapy. Recently, the radioactive tracer 111 In-girentuximab- F(ab’) 2 was developed and validated to target CAIX for SPECT imaging. The aim of this study was to optimize quantitative microSPECT/CT of CAIX in an in vivo head Athymic mice with a subcutaneous SCCNij153 and SCCNij202 head and neck carcinoma xenografts were imaged using a microSPECT/CT. First the optimal timing and protein dose for imaging were determined. Subsequently, different acquisition settings during SPECT imaging were tested. Quantification of SPECT scans was performed using IRW® software. Tracer uptake was also measured by analyzing ex vivo radioactivity counting and autoradiography of the tumor sections. Immunohistochemical staining was used to determine CAIX expression. Finally, spatial correlation between tracer uptake as measured with autoradiography and CAIX expression was calculated. Results Optimal microSPECT/CT images were obtained at 24 hours after injection of the tracer. A protein dose of 10 mg resulted in the highest tumor-to-blood ratio after 24 hours p.i. Ex vivo measurements showed a tumor uptake of 3.0 ± 0.9 %ID/g, and a tumor-to-blood ratio 31 ± 5,6 (SCCNij153). Quantitative analysis of the SPECT images was inline with the ex vivo measurements. Immunohistochemical, autoradiographic , and microSPECT/CT analyses of the xenografts showed a and neck tumor models. Material and Methods

distinct spatial correlation between localization of the tracer and CAIX expression. Fig 1. Tumor imaged with different imaging modalities: Immunohistochemistry image with in red CAIX expression and blue vessels (left), autoradiography (center), SPECT (right).

Conclusion Here we demonstrate that 111 In-girentuximab-F(ab’) 2 specifically targets to CAIX-expressing areas in head and neck cancer xenografts. SPECT imaging with 111 In- girentuximab-F(ab’) 2 allows quantitative assessment of CAIX expression. These results suggest that 111 In- girentuximab-F(ab’) 2 is a promising tracer to image hypoxia-induced CAIX expression. In future studies we will assess the tracer’s applicability for treatment selection and monitoring. OC-0267 Technical and biological validation of hypoxia PET imaging using [18F]fluroazomycin (FAZA) in NSCLC A. Salem 1 , D. Gorman 2 , H. Mistry 3 , L. Joseph 4 , R. Shah 5 , H. Valentine 1 , A. Jackson 2 , C.M.L. West 1 , C. Faivre-Finn 1 , J. O'Connor 1 , M.C. Asselin 2 1 University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom 2 University of Manchester, Division of Informatics- Imaging and Data Sciences, Manchester, United Kingdom 3 University of Manchester, Division of Pharmacy, Manchester, United Kingdom 4 University Hospital of South Manchester NHS Foundation Trust, Department of Pathology, Manchester, United Kingdom 5 University Hospital of South Manchester NHS Foundation Trust, Department of Cardiothoracic Surgery, Manchester, United Kingdom Purpose or Objective There is an unmet need to validate hypoxia PET to select patients for future hypoxia-targeted therapy trials. This study aimed to define optimal [ 18 F]FAZA PET acquisition and analysis in NSCLC patients and assess repeatability of hypoxic volumes (HV) and fractions (HF) using fixed and image-derived thresholds. As an exploratory objective, we compared tumor HFs from [ 18 F]FAZA PET with tissue hypoxia, quantified using the exogenous hypoxia marker pimonidazole. Material and Methods Twelve NSCLC patients underwent one ( n =6) or two ( n =6) [ 18 F]FAZA PET- CT at 0-1 h and 1.5-2.5 h post injection ( pi ); figure 1A . Seventeen tumor lesions, reference tissue (muscle) and blood (aorta) were manually contoured on CT ( figure 1B ). Maximum and mean standardized uptake values (SUV max and SUV mean ) were calculated. Tumor SUV max was divided by muscle or aorta SUV mean to derive tumor-to-muscle (TMR max ) and tumor-to-aorta (TAR max ) ratios. HVs and HFs were defined using a TMR ratio >1.2, >1.4 or >1.96 standard deviation (SD) above muscle SUV mean (image-derived threshold); figure 1C . Tumor pimonidazole immunostaining was quantified in a surgical patient subset who received oral pimonidazole 24 hours preoperatively ( n =6).