Evaluation of [111/114mIn]CHX-A"-DTPA-ZHER2:342, an Affibody ligand conjugate for targeting of HER2-expressing malignant tumors

Anna Orlova, D. Rosik, M. Sandström, H. Lundqvist, L. Einarsson, V. Tolmachev

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Aim. Radionuclide imaging of the HER2 receptor, which is a target for trastuzumab therapy, can provide important diagnostic information. Further, targeting radionuclide therapy might be an option for treatment of HER2 expressing tumors. The phage-display selected Affibody ligand ZHER2:342, which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the ZHER2:342, 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using ZHER2:342 labeled using [111In]benzy1-DTPA was reported. By changing to the CHX-A"-DTPA chelator, the stability and labeling kinetics of the radiometal-ZHER2:342 conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A"-DTPA-ZHER2:342 conjugate with 111In for diagnostic imaging and with 114mIn for locoregional radionuclide therapy. Methods. The isothiocyanate derivative of CHX-A"-DTPA was coupled to ZHER2:342 in alkaline conditions at 37 °C. The conjugate was labeled with both 111In and 114mIn and evaluated in vitro and in vivo. Results. Labeling with 111In and 114In provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for 114mIn and 111In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [111In]CHX-A"-DTPA-ZHER2:342 4 h postinjection was 10.3±3.6% IA/g and tumor-to-blood ratio about 190. Conclusion. [111In]CHX-A"-DTPA-ZHER2:342 is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with 114mIn it could also be used for locoregional treatment of HER2 expressing tumors.

Original languageEnglish
Pages (from-to)314-323
Number of pages10
JournalQuarterly Journal of Nuclear Medicine and Molecular Imaging
Issue number4
Publication statusPublished - Dec 2007
Externally publishedYes


  • Affibody molecule
  • HER2
  • Indium radioisotopes
  • Protein targeting

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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