111In-Benzyl-DTPA-ZHER2:342, an affibody-based conjugate for in vivo imaging of HER2 expression in malignant tumors

Vladimir Tolmachev, Fredrik Y. Nilsson, Charles Widström, Karl Andersson, Daniel Rosik, Lars Gedda, Anders Wennborg, Anna Orlova

Research output: Contribution to journalArticlepeer-review

Abstract

Data on expression of the HER2 (erbB-2) receptor in breast carcinoma make it possible to select the most efficient treatment. There are strong indications that HER2 expression possesses prognostic and predictive values in ovarian, prostate, and lung carcinomas as well. Visualization of HER2 expression using radionuclide targeting can provide important diagnostic information. The Affibody ZHER2:342 is a short (≃7 kDa) phage-display-selected protein that binds HER2 with an affinity of 22 pmol/L. The goal of this study was to evaluate whether 111In-labeled HER2: 342 can be used for imaging of HER2 overexpression in vivo. Methods: ZHER2:342 was labeled with 111In via isothiocyanatebenzyl-DTPA (DTPA is diethylenetriaminepentaacetic acid) and the conjugate was characterized in vitro and in vivo. Results: 111In-Benzyl-DTPA-ZHER2:342 preserved the capacity to bind living HER2-expressing cells specifically. The affinity of In-benzyl-DTPA-ZHER2:342 to HER2 was 21 pmol/L according to surface plasmon resonance measurements. In nude mice bearing HER2-expressing SKOV-3 xenografts, a tumor uptake of 12% ± 3% injected activity per gram and a tumor-to-blood ratio of about 100 were obtained 4 h after injection. Tumor uptake in vivo was receptor specific, as it could be blocked with an excess of nonlabeled ZHER2:342. HER2-expressing xenografts were clearly imaged 4 h after injection using a γ-camera. Conclusion: 111In-Benzyl- DTPA-ZHER2:342 is a promising candidate for visualization of HER2 expression in carcinomas, using the single-photon detection technique.

Original languageEnglish
Pages (from-to)846-853
Number of pages8
JournalJournal of Nuclear Medicine
Volume47
Issue number5
Publication statusPublished - 1 May 2006
Externally publishedYes

Keywords

  • In
  • Affibody
  • Benzyl-DTPA
  • HER2
  • Tumor targeting

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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