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Work package 02

Bioimaging - from experimental tool to clinical applicability

Objectives
To study abnormal tumour biology in preclinical models and cancer patients using PET bioimaging tracers (nitroimidazoles and other hypoxia specific PET tracers eg. 18F-FMISO, 18F-FAZA, 64Cu-ATSM, 62Cu-ATSM, 18F-EF-5) in order to estimate cellular heterogeneity within imaging voxels. Such data form the basis for exploring construction of optimal individualized dose painting in radiotherapy.
Description of work
Task 2.1. Dynamic PET scans and PET scan repeatability. Using SiHa and FaDudd xenograft tumour models confounding effects inherent to low resolution PET, slow tracer binding rates and clearance of unbound tracers from non-target tumour sub-volumes will be studied by applying dynamic scans and kinetic modeling of tissue time activity curves. Dynamic scans will be investigated using an intratumoural PET-visible reference system that allows retrieval of tumour regions of interest during post-scan analysis. Scan-to-scan repeatability will be assessed at baseline and during irradiation. Part of this task in done within the framework of BIOCARE, EU 6 FP, and METOXIA, EU 7 FP.
Task 2.2. Multitracer PET imaging. Assess, preclinically, the value of combining tracers of hypoxia (18F-FMISO,18F-FAZA,64Cu-ATSM,62Cu-ATSM,18F-EF-5), perfusion (H215O), proliferation (18F-FLT) and metabolism (18F-FDG, 11C-Methionine). Combining multiple PET tracer molecular imaging may produce a more robust prognostic 4D PET bioimage signature or single out key candidate tracers for clinical application.
Task 2.3. Correlation of PET hypoxia imaging with tumour radiobiology. Autoradiography of the above listed PET tracers will be compared directly with radiobiological hypoxia, and imunohistochemical staining including fluorescence microscopy mapping of pimonidazole (hypoxia), Hoechst-33342 (blood flow) and vessels (angiogenesis) at baseline and under modifiable hypoxia in mouse and canine tumours. 
Task 2.4. Diagnostic Molecular Bioimaging in Radiotherapy. The impact of PET/CT molecular imaging on diagnosis, tumour staging and target definition will be studied in patients with uterine cervix cancer and canine tumour patients. MRI/MRS and histopathology will serve as references.  
Task 2.5. Prognostic value of hypoxia-imaging. The prognostic and predictive value of a range of clinically approved hypoxia specific PET/CT-imaging protocols will be studied both in preclinical animal models and patients treated by curative intended radiotherapy.
Deliverables (projected outcome)
D2.1. Defining the added value of dynamic PET hypoxia scans & the impact of scan repeatability on treatment-decision making.
D2.2. Defining multi-tracer scan protocols and select key-candidate tracers for clinical application.
D2.3. Correlate PET hypoxia specific imaging with classical hypoxia-specific techniques.
D2.4. Defining the impact of PET/CT molecular imaging on diagnosis and staging
D2.5. Defining the prognostic value of PET/CT bioimaging protocols in cancer patient.

Workpackage leader: Marianne Nordsmark, AUH

Involved scientists:
Morten Busk, AUH
Kasper Toustrup, AUH
Anders Elias Hansen, KU/Life