Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 37, Issue 7, pp 1356-1367

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

  • Vladimir TolmachevAffiliated withDivision of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala UniversityDivision of Nuclear Medicine, Department of Medical Sciences, Uppsala University Email author 
  • , Irina VelikyanAffiliated withDepartment of Biochemistry and Organic Chemistry, Uppsala UniversityUppsala Applied Science Lab, GEMS PET Systems, GE Healthcare
  • , Mattias SandströmAffiliated withHospital Physics, Department of Oncology, Uppsala University Hospital
  • , Anna OrlovaAffiliated withDivision of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University

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Abstract

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, 111In-DOTA-ZHER2:342-pep2 (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positron-emitting nuclide 68Ga instead of 111In might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize 68Ga-labelled ABY-002.

Methods

68Ga labelling of ABY-002 was optimized. In vitro cell binding and procession of 68Ga-ABY-002 was evaluated. Biodistribution and tumour targeting of 68Ga-ABY-002 and 111In-ABY-002 was compared in vivo by paired-label experiments.

Results

ABY-002 was incubated with 68Ga 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 68Ga-ABY-002 and 111In-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 68Ga-ABY-002 compared with 111In-ABY-002 favouring imaging shortly after injection. For 68Ga-ABY-002, 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

68Ga-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.

Keywords

Affibody molecule HER2 68Ga Tumour targeting Molecular imaging