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@ARTICLE{Lurje:309673,
      author       = {I. Lurje and W. Werner and N. Hilbert and A.-M. Mohan and
                      K. Reers and A. Schlutt and M. Kuzminskaya and Y. Shevchenko
                      and L. Wiering and I. Eichhorn and W. Brenner$^*$ and N.
                      Beindorff and F. Tacke and L. Hammerich},
      title        = {{Q}uantification of overall tumor burden using longitudinal
                      magnetic resonance imaging improves response assessment in
                      orthotopic murine hepatocellular carcinoma models.},
      journal      = {Scientific reports},
      volume       = {16},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2026-00295},
      pages        = {5247},
      year         = {2026},
      note         = {#DKTKZFB9# / #NCTZFB9#},
      abstract     = {Hepatocellular carcinoma (HCC) is one of the most frequent
                      causes of cancer-related death worldwide.Mirroring the
                      complexity of human HCC with its underlying liver disease
                      requires multilocularorthotopic tumor models in mice, where
                      objective tumor quantification in vivo is
                      challenging,especially longitudinally. We investigated
                      magnetic resonance imaging (MRI) to noninvasively
                      quantifyorthotopic HCC in an immunotherapy setting.
                      Orthotopic HCCs were induced in
                      diethylnitrosamine(DEN)-injected mice with either
                      CCl4-induced hepatic fibrosis or dietary metabolic
                      dysfunctionassociated steatotic liver disease (MASLD) to
                      mirror the most frequent etiologies. Growth kineticsover the
                      course of immune checkpoint inhibitor treatment with
                      anti-Programmed Death Ligand1 (αPD-L1) were modeled by
                      measuring the overall tumor burden (OTB) using MRI and
                      comparedto untreated animals. Tumor parameters, such as
                      tumor volume, liver weights at sacrifice andlargest tumor
                      diameter were analyzed. We demonstrate that MRI is a
                      reliable imaging tool for bothpretreatment tumor
                      confirmation as well as the longitudinal quantification of
                      overall tumor burdenunder investigational treatment. While
                      measuring only the largest tumor diameter yielded
                      significantdifferences between αPD-L1-treated animals and
                      untreated controls in the long-term setting,these trends in
                      tumor response were not confirmed by MRI-based OTB
                      measurement. In MASLDHCC, tumors did not respond to PD-L1
                      blockade, thus confirming the OTB data and reflecting
                      theimmunotherapy resistance observed in the human setting
                      and highlighting the translational relevanceof the model.
                      Orthotopic fibrosis-HCC and MASLD-HCC mouse models can be
                      enhanced through thelongitudinal use of MRI while reducing
                      endpoints and animal numbers. The DEN-CCl4 and
                      DEN-WesternDiet models mirror the αPD-L1 response from the
                      human setting and require OTB measurement,because largest
                      diameters may underestimate the total tumor mass in
                      orthotopic HCC.},
      cin          = {BE01 / BR01},
      ddc          = {600},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)BR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41644986},
      doi          = {10.1038/s41598-026-38125-2},
      url          = {https://inrepo02.dkfz.de/record/309673},
}