Disruption of HER2 signalling by the monoclonal antibody trastuzumab or the tyrosine kinase inhibitor lapatinib improves survival of patients with metastatic breast

Purpose Overexpression of HER2 receptors is a prognostic and predictive biomarker in breast cancer and a number of other malignancies. Radionuclide molecular imaging of HER2 overexpression may influence patient management making treatment more personalized. Earlier, In-DOTA-ZHER2:342-pep2 (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positronemitting nuclide Ga instead of In might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize Ga-labelled ABY-002. Methods Ga labelling of ABY-002 was optimized. In vitro cell binding and procession of Ga-ABY-002 was evaluated. Biodistribution and tumour targeting of Ga-ABY-002 and In-ABY-002 was compared in vivo by paired-label experiments. Results ABY-002 was incubated with Ga at 90°C for 10 min resulting in a radiochemical labelling yield of over 95%. Capacity for specific binding to HER2-expressing cells was retained. In vivo, both Ga-ABY-002 and In-ABY002 demonstrated specific targeting of SKOV-3 xenografts and high-contrast imaging. Background radioactivity in blood, lungs, gastrointestinal tract and muscle fell more rapidly for Ga-ABY-002 compared with In-ABY-002 favouring imaging shortly after injection. For Ga-ABY002, a tumour uptake of 12.4±3.8%ID/g and a tumour to blood ratio of 31±13 were achieved at 2 h post-injection. Conclusion Ga-ABY-002 is easy to label and provides high-contrast imaging within 2 h after injection. This makes it a promising candidate for clinical molecular imaging of HER2 expression in malignant tumours.