On the selection of a tracer for PET imaging of HER2-expressing tumors: direct comparison of 124I-labelled Affibody molecule and trastuzumab in a murine xenograft model
2009 (English)In: European Journal of Nuclear Medicine, ISSN 0340-6997, E-ISSN 1432-105x, Vol. 50, no 3, 417-425 p.Article in journal (Refereed) Published
Human epidermal growth factor receptor type 2 (HER2) is a tyrosine kinase, which is often overexpressed in many carcinomas. Imaging HER2 expression in malignant tumors can provide important prognostic and predictive diagnostic information. The use of anti-HER2 tracers labeled with positron-emitting radionuclides may increase the sensitivity of HER2 imaging. The goal of this study was to compare directly 2 approaches for developing anti-HER2 PET tracers: a (124)I-labeled monoclonal antibody and a small (7-kDa) scaffold protein, the Affibody molecule. METHODS: The anti-HER2 Affibody Z(HER2:342) and humanized monoclonal antibody trastuzumab were labeled with (124/125)I using p-iodobenzoate (PIB) as a linker. Cellular processing of both tracers by HER2-expressing cells was investigated. The biodistributions of (124)I-PIB-Z(HER2:342) and (125)I-PIB-trastuzumab were compared in BALB/C nu/nu mice bearing HER2-expressing NCI-N87 xenografts using paired labels. Small-animal PET of (124)I-PIB-Z(HER2:342) and (124)I-PIB-trastuzumab in tumor-bearing mice was performed at 6, 24, and 72 h after injection. RESULTS: Both radioiodinated Z(HER2:342) and trastuzumab bound specifically to HER2-expressing cells in vitro and specifically targeted HER2-expressing xenografts in vivo. Radioiodinated trastuzumab was more rapidly internalized and degraded, which resulted in better retention of radioactivity delivered by Z(HER2:342). Total uptake of trastuzumab in tumors was higher than that of (124)I-PIB-Z(HER2:342). However, tumor-to-organ ratios were appreciably higher for (124)I-PIB-Z(HER2:342) due to the more rapid clearance of radioactivity from blood and normal organs. The ex vivo results were confirmed by small-animal PET. CONCLUSION: The use of the small scaffold targeting Affibody provides better contrast in HER2 imaging than does the monoclonal antibody.
Place, publisher, year, edition, pages
2009. Vol. 50, no 3, 417-425 p.
Affibody molecules, imaging, targeting, xenografts, HER2
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-104578DOI: 10.2967/jnumed.108.057919ISI: 000264084500021PubMedID: 19223403OAI: oai:DiVA.org:uu-104578DiVA: diva2:219956