Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [ 99m Tc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.
Keyphrases
- high resolution
- computed tomography
- poor prognosis
- mouse model
- papillary thyroid
- squamous cell carcinoma
- magnetic resonance imaging
- positron emission tomography
- small cell lung cancer
- cell therapy
- fluorescence imaging
- binding protein
- magnetic resonance
- stem cells
- cross sectional
- pet ct
- image quality
- small molecule
- skeletal muscle
- dual energy
- contrast enhanced
- bone marrow
- lymph node metastasis
- mesenchymal stem cells
- loop mediated isothermal amplification
- long non coding rna
- photodynamic therapy
- clinical evaluation
- wild type
- replacement therapy
- sensitive detection