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Application Note - Preclinical Imaging

Using Albira Si to Study Triple-Negative Breast Cancer

A new study by Wang et al. sought to examine the effect of non-invasive imaging with Bruker BioSpin’s Albira Si microPET/SPECT/CT system for the quantification of AXL expression after therapeutic attenuation. In basic terms, researchers wanted to monitor the effect of a specific pharmacological treatment on the overexpression of AXL in TNBC.

 

More than 250,000 cases of invasive breast cancer and 63,000 cases of noninvasive breast cancer are expected to be diagnosed in 2017, representing a steady rise in an already growing public health threat. Triple-negative breast cancer (TNBC), which can be difficult to manage with traditional hormone therapies, has been the subject of heated research in the field of oncology.
 
Targeted pharmacological therapy, which relies on downregulating certain overexpressed enzymes involved in TNBC (namely AXL receptor tyrosine kinase), may be a potential treatment strategy. Imaging with microPET/SPECT/CT systems, like Bruker BioSpin’s Albira Si, may provide insight into the downregulation response to therapeutic intervention.
 

The Importance of a Targeted Therapy Approach in TNBC

 
Targeted approaches in cancer therapy may help prevent metastasis, possibly reducing subsequent mortality. The use of imaging systems may help clinicians determine biological response to targeted therapy, thereby providing an optimized approach to cancer treatment.
 
Metastasis and treatment failure in breast cancer is sometimes associated with the activation of epithelial-to-mesenchymal transition (EMT), which occurs when epithelial cells lose cell-cell polarity and adhesion. A regulator of EMT is AXL, an enzyme which is often overexpressed in TNBC. Researchers hypothesize that AXL represents a potential target for TNBC.
 
A new study by Wang et al. sought to examine the effect of non-invasive imaging with Bruker BioSpin’s Albira Si microPET/SPECT/CT system for the quantification of AXL expression after therapeutic attenuation. In basic terms, researchers wanted to monitor the effect of a specific pharmacological treatment on the overexpression of AXL in TNBC.
 
Bruker BioSpin’s Albira Si features a resolution of up to 90 μm for CT imaging acquisition and 0.7 mm for PET in a total of three axes. In this study, researchers utilized the Albira Si platform for the imaging and assessment of AXL expression and the response to tanespimycin administration in TNBC. This type of imaging may help in identifying not only response to therapy, but it may also help guide treatment protocol for treatment optimization.
 

Researchers use microPET/SPECT/CT Imaging During TNBC Therapy

 
For the downregulation of AXL expression, researchers chose tanespimycin (17-AAG). Bruker BioSpin’s Albira Si system was used along with copper-labeled anti-AXL antibody for imaging the downregulated pattern of AXL.
 
Mice were injected with either copper-anti-AXL or copper-IgG and underwent a 15-minute PET/CT scan with Albira Si. Imaging with the Albira Si platform revealed that there was an observable downregulation of AXL expression via administration of tanespimycin.
 
Researchers also discovered tanespimycin injection correlated with reduced cell migration. When compared with control, microPET/SPECT/CT demonstrated a lower tumor radiotracer uptake associated with tanespimycin following copper-anti-hAXL injection.
 
After analyzing the imaging findings, researchers believe downregulating AXL in TNBC is a feasible method for disease management. Although not a sole treatment for the disease, this study shows how tanespimycin administration may provide an important step in an overall approach for this type of breast cancer.
 
Imaging tumor cells with Bruker’s non-invasive Albira Si following treatment may help in determining individualized response to treatment, which can help in optimizing dosing and treatment strategy.
 

References:

  1. Estimated New Cancer Cases and Deaths for 2017. Cancer.gov. https://seer.cancer.gov/csr/1975_2014/results_single/sect_01_table.01.pdf.
  2. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Journal of Clinical Investigation. 2011;121(7):2750-2767.
  3. Palmer TD, Ashby WJ, Lewis JD, Zijlstra A. Targeting tumor cell motility to prevent metastasis. Adv Drug Deliv Rev. 2011;63(8):568-581.
  4. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nature Review Cancer. 2002;2(6):442-454.
  5. Wang W, Zhao J, Wen X, et al. MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer. Contrast Media & Molecular Imaging. 2017.
  6. AlbiraSi. Bruker. https://www.bruker.com/products/preclinical-imaging/pet-spect-ct/albirasi/overview.html.