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| Home > Publications database > Quantification of overall tumor burden using longitudinal magnetic resonance imaging improves response assessment in orthotopic murine hepatocellular carcinoma models. |
| Home > Publications database > Quantification of overall tumor burden using longitudinal magnetic resonance imaging improves response assessment in orthotopic murine hepatocellular carcinoma models. |
| Journal Article | DKFZ-2026-00295 |
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2026
Springer Nature
[London]
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.
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