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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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 (K D = 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.

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Acknowledgments

The authors appreciate the support of Affibody AB. We owe special thanks to Michael Green for constructive discussions. We also appreciate the technical assistance of Ilya Lyakhov, Monika Kuban, and Alesia Holly.

The contents of this article do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.

This research was supported in part by the Center for Cancer Research, an Intramural Research Program of the National Cancer Institute, the Imaging Probe Development Center, the National Heart, Lung, and Blood Institute, and the Breast Cancer Research Stamp Fund (awarded through competitive peer review), and was funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contracts N01-CO-12400 and N01-CO-12401.

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Correspondence to Jacek Capala.

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Kramer-Marek, G., Shenoy, N., Seidel, J. et al. 68Ga-DOTA-Affibody molecule for in vivo assessment of HER2/neu expression with PET. Eur J Nucl Med Mol Imaging 38, 1967–1976 (2011). https://doi.org/10.1007/s00259-011-1810-4

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  • DOI: https://doi.org/10.1007/s00259-011-1810-4

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