Abstract
Lymph node biopsy is employed in many cancer surgeries to identify metastatic disease and to determine cancer stage, yet morbidity and diagnostic delays associated with lymph node biopsy could be avoided if noninvasive imaging of nodal involvement were reliable. Molecular imaging has potential in this regard; however, variable delivery and nonspecific uptake of imaging tracers have made conventional approaches ineffective clinically. Here we present a method of correcting for nonspecific uptake with injection of a second untargeted tracer that allows for quantification of tumor burden in lymph nodes. We confirmed the approach in an athymic mouse model of metastatic human breast cancer by targeting epidermal growth factor receptor, a cell surface receptor overexpressed by many cancers. We observed a significant correlation between in vivo (dual-tracer) and ex vivo measures of tumor burden (r = 0.97, P < 0.01), with an ultimate sensitivity of approximately 200 cells (potentially more sensitive than conventional lymph node biopsy).
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Acknowledgements
This work was sponsored by US National Institutes of Health research grants R01 CA109558, R01 CA156177, and U54 CA151662 as well as a the Canadian Institutes of Health Research postdoctoral fellowship for K.M.T.
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K.M.T. designed the experiments, developed the kinetic modeling methodology, carried out the experiments, analyzed all imaging data and wrote the paper. K.S.S. helped design the experiments and validation procedure and helped write the paper. J.R.G. carried out much of the animal imaging and carried out all qPCR and bioluminescence imaging. S.C.K. carried out photon propagation simulations. P.J.H. analyzed all H&E stains. R.J.B. and P.A.K. provided clinical support for design and direction of the study. T.H. helped supervise the project. B.W.P. provided full support for the project and gave substantial feedback on all aspects of the project.
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Tichauer, K., Samkoe, K., Gunn, J. et al. Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging. Nat Med 20, 1348–1353 (2014). https://doi.org/10.1038/nm.3732
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DOI: https://doi.org/10.1038/nm.3732
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