A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue
2010 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 7, 1356-1367 p.Article in journal (Refereed) Published
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, (111)In-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 (68)Ga instead of (111)In might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize (68)Ga-labelled ABY-002. METHODS: (68)Ga labelling of ABY-002 was optimized. In vitro cell binding and procession of (68)Ga-ABY-002 was evaluated. Biodistribution and tumour targeting of (68)Ga-ABY-002 and (111)In-ABY-002 was compared in vivo by paired-label experiments. RESULTS: ABY-002 was incubated with (68)Ga at 90 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 (68)Ga-ABY-002 and (111)In-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 (68)Ga-ABY-002 compared with (111)In-ABY-002 favouring imaging shortly after injection. For (68)Ga-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: (68)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.
Place, publisher, year, edition, pages
2010. Vol. 37, no 7, 1356-1367 p.
Medical and Health Sciences Chemical Sciences
IdentifiersURN: urn:nbn:se:uu:diva-130216DOI: 10.1007/s00259-009-1367-7ISI: 000278833100013PubMedID: 20130858OAI: oai:DiVA.org:uu-130216DiVA: diva2:348237