A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue

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-111-DOTA-Z(HER2:342-pep2) (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positron-emitting nuclide Ga-68 instead of In-111 might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize Ga-68-labelled ABY-002. Ga-68 labelling of ABY-002 was optimized. In vitro cell binding and procession of Ga-68-ABY-002 was evaluated. Biodistribution and tumour targeting of Ga-68-ABY-002 and In-111-ABY-002 was compared in vivo by paired-label experiments. ABY-002 was incubated with Ga-68 at 90A degrees 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-68-ABY-002 and In-111-ABY-002 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-68-ABY-002 compared with In-111-ABY-002 favouring imaging shortly after injection. For Ga-68-ABY-002, a tumour uptake of 12.4 A +/- 3.8%ID/g and a tumour to blood ratio of 31 A +/- 13 were achieved at 2 h post-injection. Ga-68-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.