68Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET
| Autor: | Nalini Shenoy, Gabriela Kramer-Marek, Jurgen Seidel, Peter L. Choyke, Gary L. Griffiths, Jacek Capala |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Receptor ErbB-2 Recombinant Fusion Proteins Breast Neoplasms Gallium Radioisotopes Multimodal Imaging HER2/neu Article chemistry.chemical_compound Heterocyclic Compounds 1-Ring Mice Breast cancer In vivo Cell Line Tumor medicine DOTA Animals Humans Radiology Nuclear Medicine and imaging skin and connective tissue diseases Receptor neoplasms Regulation of gene expression biology business.industry General Medicine medicine.disease Gene Expression Regulation Neoplastic Cell Transformation Neoplastic chemistry Cell culture Positron-Emission Tomography Cancer research biology.protein Affibody molecule Female business Tomography X-Ray Computed |
| Zdroj: | European journal of nuclear medicine and molecular imaging. 38(11) |
| ISSN: | 1619-7089 |
| Popis: | 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 (68)Ga-labeled DOTA-Z(HER2:2891)-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts.DOTA-Z(HER2:2891)-Affibody molecules were labeled with (68)Ga. 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 (68)Ga-DOTA-Z(HER2:2891)-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.These results suggest that PET imaging using (68)Ga-DOTA-Z(HER2:2891)-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo. |
| Databáze: | OpenAIRE |
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