Abstract
Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. However, PDT-induced tumor hypoxia as a result of oxygen consumption and vascular damage can reduce 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. In the present study, static and dynamic 18F-FMISO PET were performed with mice bearing either U87MG or MDA-MB-435 tumor xenografts immediately before and after PDT at different time points. Significant difference in tumor hypoxia in response to PDT over time was found between the U87MG and MDA-MB-435 tumors in both static and dynamic PET. Dynamic PET with pharmacokinetics modeling further monitored the kinetics of 18F-FMISO retention to hypoxic sites after treatment. The Ki and k3 parametric analysis provided information on tumor hypoxia by distinction of the specific tracer retention in hypoxic sites from its non-specific distribution in tumor. Dynamic 18F-FMISO PET with pharmacokinetics modeling, complementary to static PET analysis, provides a potential imaging tool for more detailed and more accurate quantification of tumor hypoxia during PDT.
Highlights
Several methods exist to measure hypoxia directly or indirectly
Static and dynamic Positron emission tomography (PET) scans were performed and the latter have been analyzed with compartmental pharmacokinetic modeling to better quantitate tumor hypoxia before and after Photodynamic therapy (PDT) in different tumor models
Our results suggested that U87MG tumor was initially low to non-hypoxic, therapy-induced hypoxia developed continuously subsequent to PDT (Fig. 1)
Summary
Several methods exist to measure hypoxia directly or indirectly. The “gold standard” uses polarographic electrode needles that allow direct measure of the partial oxygen pressure (pO2)[6]. Single time point static PET imaging has been generally used in 18F-FMISO hypoxia imaging to quantify the total tracer uptake present in a given tissue[8,11,13]. It reveals tissue hypoxia at molecular level in vivo with high sensitivity and specificity[13]. Besides static PET, dynamic PET with 18F-FMISO15 has been used to assess tumor hypoxia in vivo It reveals the dynamic process of tracer uptake over time and the associated kinetics such as non-specific or specific internalization of tracer in tissue. Static and dynamic PET scans were performed and the latter have been analyzed with compartmental pharmacokinetic modeling to better quantitate tumor hypoxia before and after PDT in different tumor models
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