First clinical observations of HER2 specific [111In]ABY-025 metastatic detection capability in females with metastatic breast cancer

Objectives Tumor HER2 receptor assessment is essential for a growing arsenal of HER2 targeted therapies. A HER2 specific imaging agent non-competing with the monoclonal antibodies used for therapy could offer minimal invasive, whole body receptor assessment, even during treatment. ABY-025 is an Affibody molecule developed to target these requirements. The aim of the present work was to evaluate the tumor detecting capability of [111In]ABY-025 against FDG-PET in a first-in-human study.

Methods Five days after a [18F]FDG-PET (3h) scan 7 women with metastatic breast cancer (5 with HER2+ primary tumor) received [111In]ABY-025 followed by whole body scan at 30 min, 4, 24 and 48 hours and dual SPECT-CT scans at 4, 24 and 48 hours. Images were read side-by-side. Lesions amenable to biopsy was later analyzed using immunohistochemistry.

Results In the HER2+ group one patient surprisingly demonstrated low ABY-025 uptake similar to the HER2- group. All biopsies from this patient were negative as predicted from the images and the patient was referred to the HER2- group in which a total of 82 lesions was found by ABY-025 compared with countless using FDG-PET. In the HER2+ group 51 lesions was found by ABY-025 (WB+SPECT combined) and 53 with PET. Note: Slightly different coverage for the methods. ABY-025 detected several lesions considered likely to be metastases, but not classified as such from FDG-PET alone and not yet independently verified.

Conclusions In this initial clinical study [111In]ABY-025 was well tolerated and for the HER2+ group detected nearly as many lesions as FDG-PET despite here restricted to gamma camera technology. In HER2- lesions minor receptor expression is expected and a subset of the lesions found by FDG-PET was detected using ABY-025, but at low signal levels and with overall promising indications of in-vivo HER2-discriminative capability.

Research Support Swedish Cancer Society (Contract no 10 0255)