68Ga-DOTA-Affibody molecule for in vivo assessment of HER2/neu expression with PET

  • Gabriela Kramer-Marek
  • Nalini Shenoy
  • Jurgen Seidel
  • Gary L. Griffiths
  • Peter Choyke
  • Jacek Capala
Original Article

DOI: 10.1007/s00259-011-1810-4

Cite this article as:
Kramer-Marek, G., Shenoy, N., Seidel, J. et al. Eur J Nucl Med Mol Imaging (2011) 38: 1967. doi:10.1007/s00259-011-1810-4

Abstract

Purpose

Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used 68Ga-labeled DOTA-ZHER2:2891-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts.

Methods

DOTA-ZHER2:2891-Affibody molecules were labeled with 68Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression.

Results

The 68Ga-DOTA-ZHER2:2891-Affibody probe showed high binding affinity to MDA-MB-361 cells (KD = 1.4 ± 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 ± 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression.

Conclusion

These results suggest that PET imaging using 68Ga-DOTA-ZHER2:2891-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo.

Keywords

Affibody molecules Molecular imaging HER2/neu PET 68Ga 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Gabriela Kramer-Marek
    • 1
  • Nalini Shenoy
    • 2
  • Jurgen Seidel
    • 3
  • Gary L. Griffiths
    • 2
  • Peter Choyke
    • 3
  • Jacek Capala
    • 1
  1. 1.National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Imaging Probe Development Center, National Heart, Lung, and Blood InstituteNational Institutes of HealthRockvilleUSA
  3. 3.Molecular Imaging Program, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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