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Proc Natl Acad Sci U S A. 2013 May 28;110(22):9025-30. doi: 10.1073/pnas.1213490110. Epub 2013 May 13.

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo.

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Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.


The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model to estimate the density of receptors available for binding in the tissue. Applying this approach to mice with deep-seated gliomas that overexpress the EGF receptor produced an estimate of available receptor density of 2.3 ± 0.5 nM (n = 5), consistent with values estimated in comparative invasive imaging and ex vivo studies.


engineered proteins; molecular imaging; oncology; optical imaging; spectroscopy

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