68Ga-DOTA-Affibody molecule for in vivo assessment of HER2/neu expression with PET
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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.
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.
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.
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- 68Ga-DOTA-Affibody molecule for in vivo assessment of HER2/neu expression with PET
European Journal of Nuclear Medicine and Molecular Imaging
Volume 38, Issue 11 , pp 1967-1976
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- Affibody molecules
- Molecular imaging
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- Author Affiliations
- 1. National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA
- 2. Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, USA
- 3. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA