Proceedings of the National Academy of Sciences of the United States of America
Thayer School of Engineering
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.
Davis SC, Samkoe KS, Tichauer KM, Sexton KJ, Gunn JR, Deharvengt SJ, Hasan T, Pogue BW. Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo. Proc Natl Acad Sci U S A. 2013 May 28;110(22):9025-30. doi: 10.1073/pnas.1213490110. Epub 2013 May 13. PMID: 23671066; PMCID: PMC3670304.
Dartmouth Digital Commons Citation
Davis, Scott C.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Sexton, Kristian J.; Gunn, Jason R.; Deharvengt, Sophie J.; Hasan, Tayyaba; and Pogue, Brian W., "Dynamic Dual-Tracer MRI-Guided Fluorescence Tomography to Quantify Receptor Density In Vivo" (2013). Dartmouth Scholarship. 1580.