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

Thayer School of Engineering, Dartmouth College, Hanover, NH 03755.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2013; 110(22). DOI: 10.1073/pnas.1213490110
Source: PubMed


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.

    • "FT can resolve the molecular processes by measuring the photons over the animal surface and reconstructing the distribution of fluorescent probes three-dimensionally, but it suffers from the ill-posed problem because a small amount of valid measurement data can be obtained. Much research has been done on multispectral fluorescence tomography (MFT), including spectrally resolved emission and spectrally resolved excitation (Davis et al 2013, Zacharakis et al 2005, Zavattini et al 2006). The spectrally resolved emission methods, which have already been applied in bioluminescence tomography (BLT) (Chaudhari et al 2005), use spectrally resolved boundary measurements for the reconstruction of spatial source distributions. "
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