Joana do Mar Ferreira Machado, Robert Winzer, Rudi Apolle, Almuth Forberger, Kristof Zarschler, Torsten Knieß, Martin Kreller, Klaus Kopka, Oliver C Kiß, Jan Dominik Kuhlmann, Pauline Wimberger, Matthias Miederer, Theresa Link
We report a case that combines several aspects of molecular diagnostics and clinical follow-up with innovative imaging of [89Zr]Zr-DFO-trastuzumab positron emission computed tomography (PET/CT) to depict human epidermal growth factor receptor 2 (HER2)-targeted tracer uptake in several metastatic sites in advanced platinum-resistant high-grade serous ovarian cancer (HGSOC). A 74-year-old woman underwent this procedure, and PET/CT images were interpreted alongside conventional biomarkers [CA125 and immunohistochemistry (IHC)] and contrast-enhanced computed tomography (CE-CT). PET imaging revealed intense tracer uptake in the primary ovarian tumour site (SUVratio 13.8), with corresponding HER2 + expression (3+) observed on the IHC of the primary tumour. Moreover, moderate uptake was observed in abdominal wall metastases (SUVratio 3.6) and near-background uptake in hepatic lesions (SUVratio 1.6), consistent with image-suggestive spatial heterogeneity in HER2-targeted tracer uptake. CA125 measurements corroborated early biochemical response, with values declining from 676 to 254 U/mL after six weeks of trastuzumab deruxtecan (T-DXd) treatment as third-line therapy. Follow-up CE-CT showed qualitative regression of [89Zr]Zr-DFO-trastuzumab-avid lesions, despite non-measurable disease by RECIST and a subsequent CE-CT imaging after 20 weeks demonstrated a mixed response pattern, without a clear relationship to pre-T-DXd [89Zr]Zr-DFO-trastuzumab uptake. This case study illustrates how integrating non-invasive [89Zr]Zr-DFO-trastuzumab PET molecular imaging with conventional radiology, IHC, and biochemical markers within the clinical pathway may support individualised therapeutic decision-making.