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@ARTICLE{ParedesCisneros:153520,
      author       = {I. Paredes-Cisneros$^*$ and C. P. Karger$^*$ and P. Caprile
                      and D. Nolte and I. Espinoza and A. Gago-Arias},
      title        = {{S}imulation of hypoxia {PET}-tracer uptake in tumours:
                      {D}ependence of clinical uptake-values on transport
                      parameters and arterial input function.},
      journal      = {Physica medica},
      volume       = {70},
      issn         = {1120-1797},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2020-00307},
      pages        = {109 - 117},
      year         = {2020},
      note         = {#EA:E040#},
      abstract     = {Poor radiotherapy outcome is in many cases related to
                      hypoxia, due to the increased radioresistance of hypoxic
                      tumour cells. Positron emission tomography may be used to
                      non-invasively assess the oxygenation status of the tumour
                      using hypoxia-specific radiotracers. Quantification and
                      interpretation of these images remains challenging, since
                      radiotracer binding and oxygen tension are not uniquely
                      related. Computer simulation is a useful tool to improve the
                      understanding of tracer dynamics and its relation to
                      clinical uptake parameters currently used to quantify
                      hypoxia. In this study, a model for simulating oxygen and
                      radiotracer distribution in tumours was implemented to
                      analyse the impact of physiological transport parameters and
                      of the arterial input function (AIF) on: oxygenation
                      histograms, time-activity curves, tracer binding and
                      clinical uptake-values (tissue-to-blood ratio, TBR, and a
                      composed hypoxia-perfusion metric, FHP). Results were
                      obtained for parallel and orthogonal vessel architectures
                      and for vascular fractions (VFs) of $1\%$ and $3\%.$ The
                      most sensitive parameters were the AIF and the maximum
                      binding rate (Kmax). TBR allowed discriminating VF for
                      different AIF, and FHP for different Kmax, but neither TBR
                      nor FHP were unbiased in all cases. Biases may especially
                      occur in the comparison of TBR- or FHP-values between
                      different tumours, where the relation between measured and
                      actual AIF may vary. Thus, these parameters represent only
                      surrogates rather than absolute measurements of hypoxia in
                      tumours.},
      cin          = {E040},
      ddc          = {610},
      cid          = {I:(DE-He78)E040-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32006939},
      doi          = {10.1016/j.ejmp.2020.01.012},
      url          = {https://inrepo02.dkfz.de/record/153520},
}