On then selection of a tracer for PET imaging of HER2-expressing tumors: Direct comparison of a99mI-labeled affibody molecule and trastuzumab in a murine xenograft model

Anna Orlova, Helena Wållberg, Sharon Stone-Elander, Vladimir Tolmaehev

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

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 124l-labeled monoclonal antibody and a small (7-kDa) scaffold protein, the Affibody molecule. Method: The anti-HER2 Affibody Z HER2:342 and humanized monoclonal antibody trastuzumab were labeled with 124/125l using p-iodo- benzoate (PIB) as a linker. Cellular processing of both tracers by HER2-expressing cells was investigated. The biodistributions of 124I-PIB-ZHER2:342 and 125l-PIB-trastuzumab were compared in BALB/C nulnu mice bearing HER2-expressing NCI-N87 xenografts using paired labels. Small-animal PET of 124I-PIB- ZHER2:342 and 124l-PIB-trastuzumab in tumor-bearing mice was performed at 6, 24, and 72 h after injection. Results; Both radioiodinated ZHER2:342 and trastuzumab bound specifically to HER2-express- ing 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 ZHER2:342- Total uptake of trastuzumab in tumors was higher than that of 124I-PIB-ZHER2:342- However, tumor-to-organ ratios were appreciably higher for 124I-PIB- ZHER2:342 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. COPYRIGHT

Original languageEnglish
Pages (from-to)417-425
Number of pages9
JournalJournal of Nuclear Medicine
Volume50
Issue number3
DOIs
Publication statusPublished - 1 Mar 2009
Externally publishedYes

Keywords

  • Affibody molecules
  • HER2
  • Imaging
  • Targeting
  • Xenografts

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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