HER2-PET Imaging in HER2-low Breast Cancers

A strategy to target the oncogenic receptor HER2 using a version of the anti-HER2 therapeutic antibody trastuzumab coupled to desferrioxamine (DFO) and radiolabeled with zirconium-89 (\[89Zr\]-DFO-trastuzumab) has been successfully evaluated in our group in preclinical settings. Clinical studies by other groups in recent years have shown the potential of targeting HER2+ lesions with \[89Zr\]-DFO-trastuzumab in patients with HER2+ cancers. We now want to establish the diagnostic potential of a protocol adding \[89Zr\]-DFO-trastuzumab PET imaging to FDG PET already used in the clinic for the detection of HER2-expressing cancers, including low expression levels considered until now as HER2-negative (HER2-low, IHC score 1+ and 2+ without FISH amplification of the HER2 locus). The HER2-low status has recently gained relevance thanks to large studies showing the efficacy of immunotherapy combined with drugs such as Enhertu (trastuzumab-deruxtecan), while trastuzumab alone was traditionally only effective for HER2+ cancers (IHC score 2+/FISH+, or 3+). In particular, we aim to develop a method to assess whole-body intertumoral heterogeneity in HER2 expression in order to detect cases with heterogeneous diseases and thus better stage patients and guide the optimal choice of personalized and targeted treatment to use. More specifically, the project aims to image with \[89Zr\]-DFO-trastuzumab PET patients with cancer, particularly breast cancer, but also esophageal, gastric, ovarian, endometrial and lung cancer, and whose primary tumor status is HER2-low.