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
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.
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- "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. "
ABSTRACT: It is a challenging problem to resolve and identify drug (or non-specific fluorophore) distribution throughout the whole body of small animals in vivo. In this article, an algorithm of unmixing multispectral fluorescence tomography (MFT) images based on independent component analysis (ICA) is proposed to solve this problem. ICA is used to unmix the data matrix assembled by the reconstruction results from MFT. Then the independent components (ICs) that represent spatial structures and the corresponding spectrum courses (SCs) which are associated with spectral variations can be obtained. By combining the ICs with SCs, the recovered MFT images can be generated and fluorophore concentration can be calculated. Simulation studies, phantom experiments and animal experiments with different concentration contrasts and spectrum combinations are performed to test the performance of the proposed algorithm. Results demonstrate that the proposed algorithm can not only provide the spatial information of fluorophores, but also recover the actual reconstruction of MFT images.Physics in Medicine and Biology 08/2014; 59(17):5025. DOI:10.1088/0031-9155/59/17/5025 · 2.76 Impact Factor
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ABSTRACT: Tumor hypoxia is known to affect sensitivity to radiotherapy and promote development of metastases; therefore, the ability to image tumor hypoxia in vivo could provide useful prognostic information and help tailor therapy. We previously demonstrated in vitro evidence for selective accumulation of a gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI), a magnetic resonance imaging T 1-shortening agent, in hypoxic cells grown in tissue culture. We now report evidence for accumulation of GdDO3NI in hypoxic tumor tissue in vivo. Our data show that GdDO3NI accumulated significantly (p < 0.05) in the central, poorly perfused regions of rat prostate adenocarcinoma AT1 tumors (threefold higher concentration than for the control agent) and showed better clearance from well-perfused regions and complete clearance from the surrounding muscle tissue. Inductively coupled plasma mass spectroscopy confirmed that more GdDO3NI than control agent was retained in the central region and that more GdDO3NI was retained in the central region than at the periphery. These results show the utility of GdDO3NI to image tumor hypoxia and highlight the potential of GdDO3NI for application to image-guided interventions for radiation therapy or hypoxia-activated chemotherapy.European Journal of Biochemistry 11/2013; 19(2). DOI:10.1007/s00775-013-1058-5 · 2.54 Impact Factor
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ABSTRACT: Assessing tumor margin status during surgery is critical to ensure complete resection of cancer tissue; however, current approaches are ineffective and often result in repeat surgery. We present an optical imaging approach for margin assessment using topical application of two fluorescent stains, one targeted to a tumor biomarker and the other a nontargeted reference, to freshly excised specimens. Computing a normalized difference image from fluorescence images of the targeted and untargeted stains suppresses the confounding effects of nonspecific uptake. Applying this approach in excised breast tumor models produced promising tumor-to-normal tissue contrasts that were significantly higher than single-targeted-stain imaging.Optics Letters 12/2013; 38(23):5184-7. DOI:10.1364/OL.38.005184 · 3.29 Impact Factor
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