Tezatabep Matraxetan

Human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugates (ADCs) in breast cancer is progressing rapidly, asking for precise categorization of HER2 expression. Our aim was to explore the HER2-affibody uptake characteristics in breast cancer and to find potential biomarkers for differentiating HER2 status, in comparison with ¹⁸F-FDG PET/CT.

In this prospective study conducted from May 2024 to Jan 2025, participants with newly diagnosed breast cancer underwent both ⁶⁸Ga-HER2-affibody and ¹⁸F-FDG PET/CT examinations. The relationship between PET parameters (such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), tumor-to-background SUV ratio (TBR)) and HER2 expression statuses (HER2-zero, -low and -positive) was analyzed.

A total of 57 female participants (58 primary lesions) with newly diagnosed breast cancer were included. In the paired comparison of ⁶⁸Ga-HER2-affibody and ¹⁸F-FDG PET/CT, HER2-TBR was higher than FDG-TBR in the HER2-low and HER2-positive group, respectively (P < 0.001). HER2-SUVmax and HER2-SUVmean exhibited differences across most comparisons, especially HER2-zero vs. -low (P < 0.05). HER2-SUVmean emerged as an independent predictor (P = 0.01; OR: 2.8) for differentiating HER2-low/positive and -zero, yielding an AUC of 0.91. Under detailed HER2 immunohistochemistry, HER2-SUVmax, -SUVmean and -TBR demonstrated intergroup differences (P < 0.05).

HER2-targeted PET/CT imaging demonstrated distinct advantages over ¹⁸F-FDG PET/CT imaging in characterizing the HER2 status of primary lesions. Parameters based on HER2-affibody differed significantly among different HER2 statuses, and might be potential imaging indicators for screening patients with HER2-low/positive who could benefit from HER2-targeted ADCs.

NCT06289517 (2024-03-04).

Monoclonal antibodies have revolutionized therapies, but non-immunoglobulin scaffolds are becoming compelling alternatives owing to their adaptability. Their ability to be labeled with imaging or cytotoxic compounds and to create multimeric proteins is an attractive strategy for therapeutics. Focusing on HER2, a frequently overexpressed receptor in breast cancer, this study addresses some limitations of conventional targeting moieties by harnessing the potential of these scaffolds. HER2-binding Affimers were isolated and characterized, demonstrating potency as binding reagents and efficient internalization by HER2-overexpressing cells. Affimers conjugated with cytotoxic agent achieved dose-dependent reductions in cell viability within HER2-overexpressing cell lines. Bispecific Affimers, targeting HER2 and virus-like particles, facilitated efficient internalization of virus-like particles carrying enhanced green fluorescent protein (eGFP)-encoding RNA, leading to protein expression. Anti-HER2 affibody or designed ankyrin repeat protein (DARPin) fusion constructs with the anti-VLP Affimer further underscore the adaptability of this approach. This study demonstrates the versatility of scaffolds for precise delivery of cargos into cells, advancing biotechnology and therapeutic research.