HER2-positive tumors imaged within 1 hour using a site-specifically 11C-labeled Sel-tagged affibody molecule

J Nucl Med. 2012 Sep;53(9):1446-53. doi: 10.2967/jnumed.111.102194. Epub 2012 Aug 7.


A rapid, reliable method for distinguishing tumors or metastases that overexpress human epidermal growth factor receptor 2 (HER2) from those that do not is highly desired for individualizing therapy and predicting prognoses. In vivo imaging methods are available but not yet in clinical practice; new methodologies improving speed, sensitivity, and specificity are required.

Methods: A HER2-binding Affibody molecule, Z(HER2:342), was recombinantly fused with a C-terminal selenocysteine-containing tetrapeptide Sel-tag, allowing site-specific labeling with either (11)C or (68)Ga, followed by biodistribution studies with small-animal PET. Dosimetry data for the 2 radiotracers were compared. Imaging of HER2-expressing human tumor xenografts was performed using the (11)C-labeled Affibody molecule.

Results: Both the (11)C- and (68)Ga-labeled tracers initially cleared rapidly from the blood, followed by a slower decrease to 4-5 percentage injected dose per gram of tissue at 1 h. Final retention in the kidneys was much lower (>5-fold) for the (11)C-labeled protein, and its overall absorbed dose was considerably lower. (11)C-Z(HER2:342) showed excellent tumor-targeting capability, with almost 10 percentage injected dose per gram of tissue in HER2-expressing tumors within 1 h. Specificity was demonstrated by preblocking binding sites with excess ligand, yielding significantly reduced radiotracer uptake (P = 0.002), comparable to uptake in tumors with low HER2 expression.

Conclusion: To our knowledge, the Sel-tagging technique is the first that enables site-specific (11)C-radiolabeling of proteins. Here we present the finding that, in a favorable combination between radionuclide half-life and in vivo pharmacokinetics of the Affibody molecules, (11)C-labeled Sel-tagged Z(HER2:342) can successfully be used for rapid and repeated PET studies of HER2 expression in tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Radioisotopes
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Female
  • Gallium Radioisotopes
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isotope Labeling
  • Mice
  • Models, Molecular
  • Ovarian Neoplasms / diagnostic imaging*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Positron-Emission Tomography / methods*
  • Protein Conformation
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacokinetics
  • Selenocysteine*
  • Time Factors


  • Carbon Radioisotopes
  • Gallium Radioisotopes
  • Recombinant Fusion Proteins
  • affibody (ZHER2-342)2
  • Selenocysteine
  • Receptor, ErbB-2