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

  • Vladimir Tolmachev
  • Irina Velikyan
  • Mattias Sandström
  • Anna Orlova
Original Article

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 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Vladimir Tolmachev
    • 1
    • 2
  • Irina Velikyan
    • 3
    • 4
  • Mattias Sandström
    • 5
  • Anna Orlova
    • 1
  1. 1.Division of Biomedical Radiation Sciences, Rudbeck LaboratoryUppsala UniversityUppsalaSweden
  2. 2.Division of Nuclear Medicine, Department of Medical SciencesUppsala UniversityUppsalaSweden
  3. 3.Department of Biochemistry and Organic ChemistryUppsala UniversityUppsalaSweden
  4. 4.Uppsala Applied Science LabGEMS PET Systems, GE HealthcareUppsalaSweden
  5. 5.Hospital Physics, Department of OncologyUppsala University HospitalUppsalaSweden

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