Monitoring Tumor Hypoxia using [18F]-FMISO PET and Pharmacokinetics Modeling after Photodynamic Therapy

368 Objectives Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. Irradiation of intratumoral photosensitizers leads to the conversion of tissue oxygen into singlet oxygen with subsequent generation of cytotoxic compounds. PDT-induced tumor hypoxia as a result of oxygen consumption and vascular damage can limit the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced tumor hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. Methods Static and dynamic 18F-FMISO PET were performed sequentially with mice bearing either U87MG or MDA-MB-435 tumor xenografts immediately before and after PDT at different time points. The 18F-FMISO tumor uptake was first calculated based on the static PET data. The 18F-FMISO transportation rate between plasma, diffusive and trapping compartments (K1, k2, k3) and the influx rate (Ki) were derived from dynamic PET using irreversible two-tissue compartmental modeling. The parametric mapping of k3 and Ki was further performed to assess heterogeneity of the tumor hypoxia. The above analyses were conducted for both tumor types at different time points; the variation of different parameters over time was compared between the two tumor types. Results A significant difference (P Conclusions With its ability to monitor the change of tumor hypoxia following PDT on voxels basis, pharmacokinetic modeling with parametric mapping of 18F-FMISO PET allowed quantitative identification of the hypoxic sub-volume of a tumor in vivo. This technique provides a potentially improved imaging tool, relative to static images, to map and monitor tumor hypoxia in PDT and other anti-cancer therapies.